Oxa-azaspiro compounds having activity against pain

ABSTRACT

The present invention relates to oxa-azaspiro compounds having pharmacological activity towards the sigma (σ) receptor, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.

FIELD OF THE INVENTION

The present invention relates to new oxa-azaspiro compounds havingaffinity for sigma receptors, especially sigma-1 (σ₁) receptors, as wellas to the process for the preparation thereof, to compositionscomprising them, and to their use as medicaments.

BACKGROUND OF THE INVENTION

The search for new therapeutic agents has been greatly aided in recentyears by better understanding of the structure of proteins and otherbiomolecules associated with target diseases. One important class ofthese proteins are the sigma (σ) receptors, cell surface receptors ofthe central nervous system (CNS) which may be related to the dysphoric,hallucinogenic and cardiac stimulant effects of opioids. From studies ofthe biology and function of sigma receptors, evidence has been presentedthat sigma receptor ligands may be useful in the treatment of psychosisand movement disorders such as dystonia and tardive dyskinesia, andmotor disturbances associated with Huntington's chorea or Tourette'ssyndrome and in Parkinson's disease (Walker, J. M. et al,Pharmacological Reviews, 1990, 42, 355). It has been reported that theknown sigma receptor ligand rimcazole clinically shows effects in thetreatment of psychosis (Snyder, S. H., Largent, B. L. J. Neuropsychiatry1989, 1, 7). The sigma binding sites have preferential affinity for thedextrorotatory isomers of certain opiate benzomorphans, such as(+)SKF-10047, (+)cyclazocine, and (+)-pentazocine and also for somenarcoleptics such as haloperidol.

“The sigma receptor/s” as used in this application is/are well known anddefined using the following citation: This binding site represents atypical protein different from opioid, NMDA, dopaminergic, and otherknown neurotransmitter or hormone receptor families (G. Ronsisvalle etal. Pure Appl. Chem. 73, 1499-1509 (2001)).

The sigma receptor has at least two subtypes, which may be discriminatedby stereoselective isomers of these pharmacoactive drugs. (+)SKF-10047has nanomolar affinity for the sigma-1 (σ₁) site, and has micromolaraffinity for the sigma-2 (σ₂) site. Haloperidol has similar affinitiesfor both subtypes.

The σ₁ receptor is a non-opiaceous type receptor expressed in numerousadult mammal tissues (e.g. central nervous system, ovary, testicle,placenta, adrenal gland, spleen, liver, kidney, gastrointestinal tract)as well as in embryo development from its earliest stages, and isapparently involved in a large number of physiological functions. Itshigh affinity for various pharmaceuticals has been described, such asfor (+)SKF-10047, (+)-pentazocine, haloperidol and rimcazole, amongothers, known ligands with analgesic, anxiolytic, antidepressive,antiamnesic, antipsychotic and neuroprotective activity. σ₁ receptor isof great interest in pharmacology in view of its possible physiologicalrole in processes related to analgesia, anxiety, addiction, amnesia,depression, schizophrenia, stress, neuroprotection and psychosis [Kaiseret al (1991) Neurotransmissions 7 (1): 1-5], [Walker, J. M. et al,Pharmacological Reviews, 1990, 42, 355] and [Bowen W. D. (2000)Pharmaceutica Acta Helvetiae 74: 211-218].

The σ₂ receptor is also expressed in numerous adult mammal tissues (e.g.nervous system, immune system, endocrine system, liver, kidney). σ₂receptors can be components in a new apoptosis route that may play animportant role in regulating cell proliferation or in cell development.This route seems to consist of σ₂ receptors joined to intracellularmembranes, located in organelles storing calcium, such as theendoplasmic reticulum and mitochondria, which also have the ability torelease calcium from these organelles. The calcium signals can be usedin the signaling route for normal cells and/or in induction ofapoptosis.

Agonists of σ₂ receptors induce changes in cell morphology, apoptosis inseveral types of cell lines and regulate the expression ofp-glycoprotein mRNA, so that they are potentially useful asantineoplasic agents for treatment of cancer. In fact, σ₂ receptoragonists have been observed to induce apoptosis in mammary tumour celllines resistant to common antineoplasic agents that damage DNA. Inaddition, agonists of σ₂ receptors enhance the cytotoxic effects ofthese antineoplasic agents at concentrations in which the agonist is notcytotoxic. Thus, agonists of σ₂ receptors can be used as antineoplasicagents at doses inducing apoptosis or at sub-toxic doses in combinationwith other antineoplasic agents to revert the resistance to the drug,thereby allowing using lower doses of the antineoplasic agent andconsiderably reducing its adverse effects.

Antagonists of σ₂ receptors can prevent the irreversible motor sideeffects caused by typical neuroleptic agents. In fact, it has been foundthat antagonists of σ₂ receptors can be useful as agents for improvingthe weakening effects of delayed dyskinesia appearing in patients due tochronic treatment of psychosis with typical antipsychotic drugs, such ashaloperidol. σ₂ receptors also seem to play a role in certaindegenerative disorders in which blocking these receptors could beuseful.

Endogenous sigma ligands are not known, although progesterone has beensuggested to be one of them. Possible sigma-site-mediated drug effectsinclude modulation of glutamate receptor function, neurotransmitterresponse, neuroprotection, behavior, and cognition (Quirion, R. et al.Trends Pharmacol. Sci., 1992, 13:85-86). Most studies have implied thatsigma binding sites (receptors) are plasmalemmal elements of the signaltransduction cascade. Drugs reported to be selective sigma ligands havebeen evaluated as antipsychotics (Hanner, M. et al. Proc. Natl. Acad.Sci., 1996, 93:8072-8077). The existence of sigma receptors in the CNS,immune and endocrine systems have suggested a likelihood that it mayserve as link between the three systems.

In view of the potential therapeutic applications of agonists orantagonists of the sigma receptor, a great effort has been directed tofind selective ligands. Thus, the prior art discloses different sigmareceptor ligands.

For instance, the international patent application WO2007/098961describes 4,5,6,7 tetrahydrobenzo[b]thiophene derivatives havingpharmacological activity towards the sigma receptor.

Spiro[benzopyran] or spiro[benzofuran] derivatives were also disclosedin EP1847542 as well as pyrazole derivatives (EP1634873) withpharmacological activity on sigma receptors.

WO20091071657 discloses some tricyclic triazolic compounds althoughstructurally different to the ones of the current invention withactivity towards sigma receptors.

Nevertheless, there is still a need to find compounds havingpharmacological activity towards the sigma receptor, being botheffective, selective, and/or having good “drugabillty” properties, i.e.good pharmaceutical properties related to administration, distribution,metabolism and excretion.

Surprisingly, it has been observed that the new oxa-azaspiro compoundswith general Formula (I) show a selective affinity for σ₁ receptorranging from good to excellent. These compounds are thereforeparticularly suitable as pharmacologically active agents in medicamentsfor the prophylaxis and/or treatment of disorders or diseases related toSigma receptors.

SUMMARY OF THE INVENTION

The present invention discloses novel compounds with great affinity tosigma receptors and having high solubility in a physiological mediawhich might be used for the treatment of sigma related disorders ordiseases.

As this invention is aimed at providing a compound or a chemicallyrelated series of compounds which act as ligands of the σ₁ receptor itis a very preferred embodiment if the compound has a binding expressedas K_(i) which is preferably <1000 nM, more preferably <500 nM, evenmore preferably <100 nM.

The invention is directed in a main aspect to a compound of generalFormula (I),

-   -   wherein R₁, R₂, R₃, R_(3′), R₅, R_(5′), R₆, R_(6′), R_(n), X, Y,        m and n are as defined below in the detailed description.

A further object of the invention refers to the processes forpreparation of compounds of general formula (I).

A still further object of the invention refers to the use ofintermediate compounds for the preparation of a compound of generalformula (I).

It is also an object of the invention a pharmaceutical compositioncomprising a compound of formula (I).

Finally, it is an object of the invention the use of compound as amedicament and more particularly for the treatment of pain and painrelated conditions.

DETAILED DESCRIPTION OF THE INVENTION

The present invention discloses novel compounds with great affinity tosigma receptors and having high solubility in a physiological mediawhich might be used for the treatment of sigma related disorders ordiseases.

As this invention is aimed at providing a compound or a chemicallyrelated series of compounds which act as ligands of the σ₁ receptor itis a very preferred embodiment if the compound has a binding expressedas K_(i) which is preferably <1000 nM, more preferably <500 nM, evenmore preferably <100 nM.

Advantageously, the compounds according to the present invention wouldin addition show one or more the following functionalities: σ₁ receptorantagonism. It has to be noted, though, that the functionalities“antagonism” and “agonism” are also sub-divided in their effect intosubfunctionalities like partial agonism or inverse agonism. Accordingly,the functionalities of the compound should be considered within arelatively broad bandwidth.

An antagonist blocks or dampens agonist-mediated responses. Knownsubfunctionalities are neutral antagonists or inverse agonists.

An agonist increases the activity of the receptor above its basal level.Known subfunctionalities are full agonists, or partial agonists.

The invention is directed in a main aspect to a compound of generalFormula (I),

In a particular aspect, the present invention is directed to compoundsof general Formula (I):

m is 1, 2, 3, 4 or 5;

n is 0, 1, 2, 3, 4 or 5;

p is 0, 1 or 2;

X is a bond, —C(R_(x)R_(x′))—, —O—, —C(O)—, —C(O)NR₇—, —NR₇C(O)— or—C(O)O—;

-   -   wherein R_(x) is selected from halogen, —OR₇, substituted or        unsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆        alkenyl and substituted or unsubstituted C₂₋₆ alkynyl;

R_(x′) is selected from hydrogen, halogen, substituted or unsubstitutedC₁₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl and substituted orunsubstituted C₂₋₆ alkynyl;

R₇ is selected from hydrogen, substituted or unsubstituted C₁₋₆ alkyl,substituted or unsubstituted C₂₋₆ alkenyl and substituted orunsubstituted C₂₋₆ alkynyl;

Y is —CH₂— or —C(O)—;

R_(1′) is selected from substituted or unsubstituted C₁₋₆ alkyl,substituted or unsubstituted C₂₋₆ alkenyl, substituted or unsubstitutedC₂₋₆ alkynyl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted aryl and substituted or unsubstituted heterocyclyl;

R₂ is selected from hydrogen, substituted or unsubstituted C₁₋₆ alkyl,substituted or unsubstituted C₂₋₆ alkenyl, substituted or unsubstitutedC₂₋₆ alkynyl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted aryl and substituted or unsubstituted heterocyclyl;

R₃ and R_(3′) are independently selected from hydrogen, substituted orunsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl,substituted or unsubstituted C₂₋₆ alkynyl, substituted or unsubstitutedcycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted orunsubstituted alkylaryl, substituted or unsubstituted aryl, substitutedor unsubstituted heterocyclyl or substituted or unsubstitutedalkylheterocyclo;

alternatively R₃ and R_(3′) taken together with the connecting C-atommay form an substituted or unsubstituted cycloalkyl;

R₄ and R_(4′) are independently selected from hydrogen, substituted orunsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl andsubstituted or unsubstituted C₂₋₆ alkynyl;

R₅ and R_(5′) are independently selected from hydrogen, substituted orunsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl,substituted or unsubstituted C₂₋₆ alkynyl, substituted or unsubstitutedcycloalkyl and substituted or unsubstituted heterocyclyl;

alternatively, R₅ and R_(5′) taken together with the connecting C-atommay form an substituted or unsubstituted cycloalkyl or a substituted orunsubstituted heterocyclyl;

R₆ and R_(6′) are independently selected from hydrogen, halogen,substituted or unsubstituted C₁₋₆ alkyl, substituted or unsubstitutedC₂₋₆ alkenyl, substituted or unsubstituted C₂₋₆ alkynyl, —CHOR₈ and—C(O)OR₈;

-   -   wherein R₈ is selected from hydrogen, substituted or        unsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆        alkenyl and substituted or unsubstituted C₂₋₆ alkynyl;

R_(n) is selected from hydrogen, unsubstituted C₁₋₆ alkyl, unsubstitutedC₂₋₆ alkenyl and unsubstituted C₂₋₆ alkynyl;

These compounds according to the invention are optionally in form of oneof the stereoisomers, preferably enantiomers or diastereomers, aracemate or in form of a mixture of at least two of the stereoisomers,preferably enantiomers and/or diastereomers, in any mixing ratio, or acorresponding salt thereof, or a corresponding solvate thereof.

Thus, the compounds according to Formula (I) may take for example thefollowing stereochemical conformation:

In a further embodiment the following proviso applies:

when Y is-C(O)—; then R₁ is not

In a further embodiment the compound according to the invention ofgeneral Formula (I) is a compound of general Formula (I′)

wherein, R₁, R₂, R₃, R_(3′), R₅, R_(5′), R_(n), Y and m are as definedin the description.

In a further embodiment the compound according to the invention ofgeneral Formula (I) is a compound of general Formula (I^(a′))

wherein, R₁, R₂, R₅, R_(5′), R_(n), Y and m are as defined in thedescription.

In a further embodiment the compound according to the invention ofgeneral Formula (I) is a compound of general Formula (I^(b′))

wherein, R₁, R₂, R₅, R_(5′), R_(n), Y and m are as defined in thedescription.

In a further embodiment the compound according to the invention ofgeneral Formula (I) is a compound of general Formula (I^(2′))

wherein R₁, R₂, R₅, R_(5′), R_(n), Y and m are as defined in thedescription.

In a further embodiment, for compounds of general Formula (I) arecompounds of general Formula (I^(3′))

wherein R_(1′), R₂, R₅, R_(5′), R_(n), Y and m are as defined in thedescription.

For clarity purposes, reference is also made to the following statementsbelow in the definitions of substitutions on alkyl etc. or aryl etc.that “wherein when different radicals R₁ to R_(14″″) and R_(x), R_(x′)and R_(n) are present simultaneously in Formula I they may be identicalor different”. This statement is reflected in the below general Formula(I^(4′)) being derived from and falling into general Formula (I).

wherein R₁, R₂, R₅, R_(5′), R_(n), X and Y are as defined in thedescription. In addition, m′ (being 0 or 1), R_(5″) and R_(5′″) areadded. As said above, this statement is thus reflected in that R_(5″)and R_(5′″) are or could be different from R₅ and R_(5′) or notand—accordingly—m′ being 0 or 1 is naturally resulting from m (ingeneral Formulas (I), (I′), (I^(a′)), (I^(b′)), (I^(2′)) or (I^(3′))being 1 or 2).

The same would be applicable mutatis mutandis for general Formulas likegeneral Formula (I) as well as the other general Formulas (I′) to(I^(3′)) above as well as to all the intermediates of synthesis.

For clarity purposes, all groups and definitions described in thedescription and referring to compounds of general Formula (I), alsoapply to compounds of general Formula (I′), (I^(a′)), (I^(b′)), (I^(2′))or (I^(3′)), and also (I^(4′)), as well as to all the intermediates ofsynthesis, when those groups are present in the mentioned generalMarkush formulae, since compounds of general Formula (I′), (I^(a′)),(I^(b′)), (I^(2′)), (I^(3′)) or (I^(4′)) are included in the generalFormula (I).

For clarity purposes, the general Markush Formula (I)

is equivalent to

wherein only-C(R₅R_(5′))— and —C(R₆R_(6′))— are included into thebrackets and m and n mean the number of times that —C(R₅R_(5′))— and—C(R₆R_(6′))— are repeated, respectively. The same would apply togeneral Markush Formulae (I′), (I^(a′)), (I^(b)), (I^(2′)), (I^(3′)) or(I^(4′)) and to all the intermediates of synthesis.

In addition, and for clarity purposes, it should further be understoodthat naturally if m or n are 0, then X, —N(R_(n))— or R₂ are stillpresent in general Markush Formulae (I), (I′), (I^(a′)), (I^(b′)),(I^(2′)), (I^(3′)) or (I^(4′)) and to all the intermediates ofsynthesis.

In the context of this invention, alkyl is understood as meaningsaturated, linear or branched hydrocarbons, which may be unsubstitutedor substituted once or several times. It encompasses e.g. —CH₃ and—CH₂—CH₃. In these radicals, C₁₋₂-alkyl represents C1- or C2-alkyl,C₁₋₃-alkyl represents C1-, C2- or C3-alkyl, C₁₋₄-alkyl represents C1-,C2-, C3- or C4-alkyl, C₁₋₅-alkyl represents C1-, C2-, C3-, C4-, orC5-alkyl, C₁₋₆-alkyl represents C1-, C2-, C3-, C4-, C5- or C6-alkyl,C₁₋₇-alkyl represents C1-, C2-, C3-, C4-, C5-, C6- or C7-alkyl,C₁₋₈-alkyl represents C1-, C2-, C3-, C4-, C5-, C6-, C7- or C8-alkyl,C₁₋₁₀-alkyl represents C1-, C2-, C3-, C4-, C5-, C6-, C7-, C8-, C9- orC10-alkyl and C₁₋₁₈-alkyl represents C1-, C2-, C3-, C4-, C5-, C6-, C7-,C8-, C9-, C10-, C11-, C12-, C13-, C14-, C15-, C16-, C17- or C18-alkyl.The alkyl radicals are preferably methyl, ethyl, propyl, methylethyl,butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl,1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, hexyl,1-methylpentyl, if substituted also CHF₂, CF₃ or CH₂OH etc. Preferablyalkyl is understood in the context of this invention as C₁₋₆alkyl likemethyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, or octyl;preferably is C₁₋₆alkyl like methyl, ethyl, propyl, butyl, pentyl, orhexyl; more preferably is C₁₋₄alkyl like methyl, ethyl, propyl or butyl.

Alkenyl is understood as meaning unsaturated, linear or branchedhydrocarbons, which may be unsubstituted or substituted once or severaltimes. It encompasses groups like e.g. —CH═CH—CH₃. The alkenyl radicalsare preferably vinyl (ethenyl), allyl (2-propenyl). Preferably in thecontext of this invention alkenyl is C₂₋₁₀-alkenyl or C₂₋₈-alkenyl likeethylene, propylene, butylene, pentylene, hexylene, heptylene oroctylene; or is C₂₋₆-alkenyl like ethylene, propylene, butylene,pentylene, or hexylene; or is C₂₋₄-alkenyl, like ethylene, propylene, orbutylenes.

Alkynyl is understood as meaning unsaturated, linear or branchedhydrocarbons, which may be unsubstituted or substituted once or severaltimes. It encompasses groups like e.g. —C═C—CH₃ (1-propinyl). Preferablyalkynyl in the context of this invention is C₂₋₁₀-alkynyl orC₂₋₈-alkynyl like ethyne, propyne, butyene, pentyne, hexyne, heptyne, oroctyne; or is C₂₋₆-alkynyl like ethyne, propyne, butyene, pentyne, orhexyne; or is C₂₋₄-alkynyl like ethyne, propyne, butyene, pentyne, orhexyne.

In connection with alkyl (also in alkylaryl, alkylheterocyclyl oralkylcycloalkyl), alkenyl, alkynyl and O-alkyl—unless definedotherwise—the term substituted in the context of this invention isunderstood as meaning replacement of at least one hydrogen radical on acarbon atom by halogen (F, Cl, Br, I), —NR_(c)R_(c′″)—, —SR_(c),—S(O)R_(c), —S(O)₂R_(c), —OR_(c), —C(O)OR_(c), —CN, —C(O)NR_(c)R_(c′),haloalkyl, haloalkoxy or —OC₁₋₆ alkyl being R_(c) represented by R₁₁,R₁₂, R₁₃, (being R_(c′) represented by R_(11′), R_(12′), R_(13′); beingR_(c″) represented by R_(11″), R_(12″), R_(13″); being R_(c′″)represented by R_(11′″), R_(12′″), R_(13′″), being R_(c′″) representedby R_(11″″), R_(12″″), R_(13″″)) wherein R₁ to R_(14″″) and R_(x),R_(x′) and R_(n) are as defined in the description, and wherein whendifferent radicals R₁ to R_(14″″) and R_(x), R_(x′) and R_(n) arepresent simultaneously in Formula I they may be identical or different.

Most preferably in connection with alkyl (also in alkylaryl,alkylheterocyclo or alkylcycloalkyl), alkenyl, alkynyl or O-alkyl,substituted is understood in the context of this invention that anyalkyl (also in alkylaryl, alkylheterocyclo or alkylcycloalkyl), alkenyl,alkynyl or O-alkyl which is substituted is substituted with one or moreof halogen (F, Cl, Br, I), —OR_(c), —CN, —NR_(c)R_(c′″), haloalkyl,haloalkoxy or —OC₁₋₆alkyl, being R_(c) represented by R₁₁, R₁₂, R₁₃,(being R_(c′) represented by R_(11′), R_(12′), R_(13′); being R_(c″)represented by R_(11″), R_(12″), R_(13″); being R_(c′″) represented byR_(11′″), R_(12′″), R_(13′″), being R_(c″″) represented by R_(11″″),R_(12″″), R_(13″″)), wherein R₁ to R_(14″″) and R_(x), R_(x′) and R_(n)are as defined in the description, and wherein when different radicalsR₁ to R_(14″″) and R_(x), R_(x′) and R_(n) are present simultaneously inFormula I, they may be identical or different.

More than one replacement on the same molecule and also on the samecarbon atom is possible with the same or different substituents. Thisincludes for example 3 hydrogens being replaced on the same C atom, asin the case of CF₃, or at different places of the same molecule, as inthe case of e.g. —CH(OH)—CH═CH—CHCl₂.

In the context of this invention haloalkyl is understood as meaning analkyl being substituted once or several times by a halogen (selectedfrom F, Cl, Br, I). It encompasses e.g. —CH₂Cl, —CH₂F, —CHCl₂, —CHF₂,—CCl₃, —CF₃ and —CH₂—CHCl₂. Preferably haloalkyl is understood in thecontext of this invention as halogen-substituted C₁₋₄-alkyl representinghalogen substituted C1-, C2-, C3- or C4-alkyl. The halogen-substitutedalkyl radicals are thus preferably methyl, ethyl, propyl, and butyl.Preferred examples include —CH₂Cl, —CH₂F, —CHCl₂, —CHF₂, and —CF₃.

In the context of this invention haloalkoxy is understood as meaning an—O-alkyl being substituted once or several times by a halogen (selectedfrom F, Cl, Br, I). It encompasses e.g. —OCH₂Cl, —OCH₂F, —OCHCl₂,—OCHF₂, —OCCl₃, —OCF₃ and —OCH₂—CHCl₂. Preferably haloalkyl isunderstood in the context of this invention as halogen-substituted—OC₁₋₄-alkyl representing halogen substituted C1-, C2-, C3- orC4-alkoxy. The halogen-substituted alkyl radicals are thus preferablyO-methyl, O-ethyl, O-propyl, and O-butyl. Preferred examples include—OCH₂Cl, —OCH₂F, —OCHCl₂, —OCHF₂, and —OCF₃.

In the context of this invention cycloalkyl is understood as meaningsaturated and unsaturated (but not aromatic) cyclic hydrocarbons(without a heteroatom in the ring), which can be unsubstituted or onceor several times substituted. Furthermore, C₃₋₄-cycloalkyl representsC3- or C4-cycloalkyl, C₃₋₅-cycloalkyl represents C3-, C4- orC5-cycloalkyl, C₃₋₆-cycloalkyl represents C3-, C4-, C5- orC6-cycloalkyl, C₃₋₇-cycloalkyl represents C3-, C4-, C5-, C6- orC7-cycloalkyl, C₃₋₈-cycloalkyl represents C3-, C4-, C5-, C6-, C7- orC8-cycloalkyl, C₄₋₅-cycloalkyl represents C4- or C5-cycloalkyl,C₄₋₆cycloalkyl represents C4-, C5- or C6-cycloalkyl, C₄₋₇-cycloalkylrepresents C4-, C5-, C6- or C7-cycloalkyl, C₅₋₆-cycloalkyl representsC5- or C6-cycloalkyl and C₅₋₇-cycloalkyl represents C5-, C6- orC7-cycloalkyl. Examples are cyclopropyl, 2-methylcyclopropyl,cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclopentylmethyl,cyclohexyl, cycloheptyl, cyclooctyl, and also adamantly. Preferably inthe context of this invention cycloalkyl is C₃₋₈cycloalkyl likecyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, orcyclooctyl; or is C₃₋₇cycloalkyl like cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, or cycloheptyl; or is C₃₋₆cycloalkyl likecyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, especiallycyclopentyl or cyclohexyl.

Aryl is understood as meaning 5 to 18 membered mono or polycyclic ringsystems with at least one aromatic ring but without heteroatoms even inonly one of the rings. Examples are phenyl, naphthyl, fluoranthenyl,fluorenyl, tetralinyl or indanyl, 9H-fluorenyl or anthracenyl radicals,which can be unsubstituted or once or several times substituted. Mostpreferably aryl is understood in the context of this invention asphenyl, naphtyl or anthracenyl, preferably is phenyl.

A heterocyclyl radical or group (also called heterocyclyl hereinafter)is understood as meaning 5 to 18 membered mono or polycyclicheterocyclic ring systems, with at least one saturated or unsaturatedring which contains one or more heteroatoms from the group consisting ofnitrogen, oxygen and/or sulfur in the ring. A heterocyclic group canalso be substituted once or several times.

Examples include non-aromatic heterocyclyls such as tetrahydropyrane,oxazepane, morpholine, piperidine, pyrrolidine as well as heteroarylssuch as furan, benzofuran, thiophene, benzothiophene, pyrrole, pyridine,pyrimidine, pyrazine, quinoline, isoquinoline, phthalazine, thiazole,benzothiazole, indole, benzotriazole, carbazole and quinazoline.

Subgroups inside the heterocyclyls as understood herein includeheteroaryls and non-aromatic heterocyclyls.

-   -   the heteroaryl (being equivalent to heteroaromatic radicals or        aromatic heterocyclyls) is an aromatic 5 to 18 membered mono or        polycyclic heterocyclic ring system of one or more rings of        which at least one aromatic ring contains one or more        heteroatoms from the group consisting of nitrogen, oxygen and/or        sulfur in the ring; preferably is an aromatic 5 to 18 membered        mono or polycyclic heterocyclic ring system of one or two rings        of which at least one aromatic ring contains one or more        heteroatoms from the group consisting of nitrogen, oxygen and/or        sulfur in the ring, more preferably is selected from furan,        benzofuran, thiophene, benzothiophene, pyrrole, pyridine,        pyrimidine, pyrazine, quinoline, isoquinoline, phthalazine,        benzothiazole, indole, benzotriazole, carbazole, quinazoline,        thiazole, imidazole, pyrazole, oxazole, thiophene and        benzimidazole;    -   the non-aromatic heterocyclyl is a 5 to 18 membered mono or        polycyclic heterocyclic ring system of one or more rings of        which at least one ring        -   with this (or these) ring(s) then not being            aromatic—contains one or more heteroatoms from the group            consisting of nitrogen, oxygen and/or sulfur in the ring;            preferably is a 5 to 18 membered mono or polycyclic            heterocyclic ring system of one or two rings of which one or            both rings—with this one or two rings then not being            aromatic—contain/s one or more heteroatoms from the group            consisting of nitrogen, oxygen and/or sulfur in the ring,            more preferably is selected from oxazepam, pyrrolidine,            piperidine, piperazine, tetrahydropyran, morpholine,            indoline, oxopyrrolidine, benzodioxane, oxetane, especially            is benzodioxane, morpholine, tetrahydropyran, piperidine,            oxopyrrolidine, oxetane and pyrrolidine.

Preferably in the context of this invention heterocyclyl is defined as a5 to 18 membered mono or polycyclic heterocyclic ring system of one ormore saturated or unsaturated rings of which at least one ring containsone or more heteroatoms from the group consisting of nitrogen, oxygenand/or suitor in the ring. Preferably it is a 5 to 18 membered mono orpolycyclic heterocyclic ring system of one or two saturated orunsaturated rings of which at least one ring contains one or moreheteroatoms from the group consisting of nitrogen, oxygen and/or sulfurin the ring.

Preferred examples of heterocyclyls include oxetane, oxazepan,pyrrolidine, imidazole, oxadiazole, tetrazole, pyridine, pyrimidine,piperidine, piperazine, benzofuran, benzimidazole, indazole,benzodiazole, thiazole, benzothiazole, tetrahydropyrane, morpholine,indoline, furan, triazole, isoxazole, pyrazole, thiophene,benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline,isoquinoline, phthalazine, benzo-1,2,5-thiadiazole, indole,benzotriazole, benzoxazole oxopyrrolidine, pyrimidine, benzodioxolane,benzodioxane, carbazole and quinazoline, especially is pyridine,pyrazine, indazole, benzodioxane, thiazole, benzothiazole, morpholine,tetrahydropyrane, pyrazole, imidazole, piperidine, thiophene, indole,benzimidazole, pyrrolo[2,3b]pyridine, benzoxazole, oxopyrrolidine,pyrimidine, oxazepane, oxetane and pyrrolidine.

In the context of this invention oxopyrrolidine is understood as meaningpyrrolidin-2-one.

In connection with aromatic heterocyclyls (heteroaryls), non-aromaticheterocyclyls, aryls and cycloalkyls, when a ring system falls withintwo or more of the above cycle definitions simultaneously, then the ringsystem is defined first as an aromatic heterocyclyl (heteroaryl) if atleast one aromatic ring contains a heteroatom. If no aromatic ringcontains a heteroatom, then the ring system is defined as a non-aromaticheterocyclyl if at least one non-aromatic ring contains a heteroatom. Ifno non-aromatic ring contains a heteroatom, then the ring system isdefined as an aryl if it contains at least one aryl cycle. If no aryl ispresent, then the ring system is defined as a cycloalkyl if at least onenon-aromatic cyclic hydrocarbon is present.

In the context of this invention alkylaryl is understood as meaning anaryl group (see above) being connected to another atom through aC₁₋₆-alkyl (see above) which may be branched or linear and isunsubstituted or substituted once or several times. Preferably alkylarylis understood as meaning an aryl group (see above) being connected toanother atom through 1 to 4 (—CH₂—) groups. Most preferably alkylaryl isbenzyl (i.e. —CH₂-phenyl).

In the context of this invention alkylheterocyclyl is understood asmeaning an heterocyclyl group being connected to another atom through aC₁₋₆-alkyl (see above) which may be branched or linear and isunsubstituted or substituted once or several times. Preferablyalkylheterocyclyl is understood as meaning an heterocyclyl group (seeabove) being connected to another atom through 1 to 4 (—CH₂—) groups.Most preferably alkylheterocyclyl is —CH₂-pyridine.

In the context of this invention alkylcycloalkyl is understood asmeaning an cycloalkyl group being connected to another atom through aC₁₋₆-alkyl (see above) which may be branched or linear and isunsubstituted or substituted once or several times. Preferablyalkylcycloalkyl is understood as meaning an cycloalkyl group (see above)being connected to another atom through 1 to 4 (—CH₂—) groups. Mostpreferably alkylcycloalkyl is —CH₂-cyclopropyl.

Preferably, the aryl is a monocyclic aryl. More preferably the aryl is a5, 6 or 7 membered monocyclic aryl. Even more preferably the aryl is a 5or 6 membered monocyclic aryl.

Preferably, the heteroaryl is a monocyclic heteroaryl. More preferablythe heteroaryl is a 5, 6 or 7 membered monocyclic heteroaryl. Even morepreferably the heteroaryl is a 5 or 6 membered monocyclic heteroaryl.

Preferably, the non-aromatic heterocyclyl is a monocyclic non-aromaticheterocyclyl. More preferably the non-aromatic heterocyclyl is a 4, 5, 6or 7 membered monocyclic non-aromatic heterocyclyl. Even more preferablythe non-aromatic heterocyclyl is a 5 or 6 membered monocyclicnon-aromatic heterocyclyl.

Preferably, the cycloalkyl is a monocyclic cycloalkyl. More preferablythe cycloalkyl is a 3, 4, 5, 6, 7 or 8 membered monocyclic cycloalkyl.Even more preferably the cycloalkyl is a 3, 4, 5 or 6 memberedmonocyclic cycloalkyl.

In connection with aryl (including alkyl-aryl), cycloalkyl (includingalkylcycloalkyl), or heterocyclyl (including alkyl-heterocyclyl),substituted is understood—unless defined otherwise—as meaningsubstitution of the ring-system of the aryl or alkyl-aryl, cycloalkyl oralkyl-cycloalkyl; heterocyclyl or alkyl-heterocyclyl with one or more ofhalogen (F, Cl, Br, I), —R_(c), —OR_(c), —OR_(c), —NO₂, —NR_(c)R_(c′″),—C(O)OR_(c), NR_(c)C(O)R_(c′), —C(O)NR_(c)R_(c′), —NR_(c)S(O)₂R_(c′),═O, —OCH₂CH₂OH, —NR_(c)C(O)NR_(c′)R_(c″), —S(O)₂NR_(c)R_(c′),—NR_(c)S(O)₂NR_(c′)R_(c″), haloalkyl, haloalkoxy, —SR_(c), —S(O)R_(c),—S(O)₂R_(c) or C(CH₃)OR_(c); NR_(c)R_(c′″), with R_(c), R_(c′), R_(c″)and R_(c′″) independently being either H or a saturated or unsaturated,linear or branched, substituted or unsubstituted C₁₋₆-alkyl; a saturatedor unsaturated, linear or branched, substituted or unsubstitutedC₁₋₆-alkyl; a saturated or unsaturated, linear or branched, substitutedor unsubstituted —O—C₁₋₆-alkyl (alkoxy); a saturated or unsaturated,linear or branched, substituted or unsubstituted —S—C₁₋₆-alkyl; asaturated or unsaturated, linear or branched, substituted orunsubstituted —C(O)—C₁₋₆-alkyl-group; a saturated or unsaturated, linearor branched, substituted or unsubstituted —C(O)—O—C₁₋₆-alkyl-group; asubstituted or unsubstituted aryl or alkyl-aryl; a substituted orunsubstituted cycloalkyl or alkyl-cycloalkyl; a substituted orunsubstituted heterocyclyl or alkyl-heterocyclyl, being R_(c) one ofR₁₁, R₁₂ or R₁₄, (being R_(c′) one of R_(11′), R_(12′) or R_(14′); beingR_(c″) one of R_(11′), R_(12′) or R_(14″); being R_(c′″) one ofR_(11′″), R_(12′″) or R_(14′″); being R_(c″″) one of R_(11″″), R_(12″″)or R_(14″″)), wherein R₁ to R_(14″″) and R_(x), R_(x′) and R_(n) are asdefined in the description, and wherein when different radicals R₁ toR_(14″″) and R_(x), R_(x′) and R_(n) are present simultaneously inFormula I they may be identical or different.

Most preferably in connection with aryl (including alkyl-aryl),cycloalkyl (including alkyl-cycloalkyl), or heterocyclyl (includingalkyl-heterocyclyl), substituted is understood in the context of thisinvention that any aryl, cycloalkyl and heterocyclyl which issubstituted is substituted (also in an alyklaryl, alkylcycloalkyl oralkylheterocyclo) with one or more of halogen (F, Cl, Br, I), —R_(c),—OR_(c), —CN, —NO₂, —NR_(c)R_(c′″), NR_(c)C(O)R_(c′),—NR_(c)S(O)₂R_(c′), ═O, haloalkyl, haloalkoxy, or C(CH₃)OR_(c);—OC₁₋₄alkyl being unsubstituted or substituted with one or more ofOR_(c) or halogen (F, Cl, I, Br), —CN, or —C₁₋₄alkyl being unsubstitutedor substituted with one or more of OR_(c) or halogen (F, Cl, I, Br),being R_(c) one of R₁₁, R₁₂ or R₁₄, (being R_(c′) one of R_(11′),R_(12′) or R_(14′); being R_(c″) one of R_(11″), R_(12″) or R_(14″);being R_(c′″) one of R_(11′″), R_(12′″) or R_(14′″); being R_(c″″) oneof R_(11′″), R_(12″″) or R_(14″″)), wherein R₁ to R_(14″″) and R_(x),R_(x′) and R_(n) areas defined in the description, and wherein whendifferent radicals R₁ to R_(14″″) and R_(x), R_(x′) and R_(n) arepresent simultaneously in Formula I they may be identical or different.

Additionally to the above-mentioned substitutions, in connection withcycloalkyl (including alkyl-cycloalkyl), or heterocycly (includingalkylheterocyclo) namely non-aromatic heterocyclyl (includingnon-aromatic alkyl-heterocyclyl), substituted is also understood—unlessdefined otherwise—as meaning substitution of the ring-system of thecycloalkyl or alkyl-cycloalkyl; non-aromatic heterocyclyl or nonaromatic alkyl-heterocyclyl with

A ring system is a system consisting of at least one ring of connectedatoms but including also systems in which two or more rings of connectedatoms are joined with “joined” meaning that the respective rings aresharing one (like a spiro structure), two or more atoms being a memberor members of both joined rings.

The term “leaving group” means a molecular fragment that departs with apair of electrons in heterolytic bond cleavage. Leaving groups can beanions or neutral molecules. Common anionic leaving groups are halidessuch as Cl—, Br—, and I—, and sulfonate esters, such as tosylate (TsO—)or mesylate.

The term “salt” is to be understood as meaning any form of the activecompound used according to the invention in which it assumes an ionicform or is charged and is coupled with a counter-ion (a cation or anion)or is in solution. By this are also to be understood complexes of theactive compound with other molecules and ions, in particular complexesvia ionic interactions.

The term “physiologically acceptable salt” means in the context of thisinvention any salt that is physiologically tolerated (most of the timemeaning not being toxic-especially not caused by the counter-ion) ifused appropriately for a treatment especially if used on or applied tohumans and/or mammals.

These physiologically acceptable salts can be formed with cations orbases and in the context of this invention is understood as meaningsalts of at least one of the compounds used according to theinvention—usually a (deprotonated) add—as an anion with at least one,preferably inorganic, cation which is physiologicallytolerated—especially if used on humans and/or mammals. The salts of thealkali metals and alkaline earth metals are particularly preferred, andalso those with NH₄, but in particular (mono)- or (di)sodium, (mono)- or(di)potassium, magnesium or calcium salts.

Physiologically acceptable salts can also be formed with anions or addsand in the context of this invention is understood as meaning salts ofat least one of the compounds used according to the invention as thecation with at least one anion which are physiologicallytolerated—especially if used on humans and/or mammals. By this isunderstood in particular, in the context of this invention, the saltformed with a physiologically tolerated add, that is to say salts of theparticular active compound with inorganic or organic adds which arephysiologically tolerated—especially if used on humans and/or mammals.Examples of physiologically tolerated salts of particular adds are saltsof: hydrochloric add, hydrobromic add, sulfuric add, methanesulfonicadd, formic add, acetic acid, oxalic acid, succinic acid, malic add,tartaric add, mandelic add, fumaric add, lactic add or citric add.

The compounds of the invention may be present in crystalline form or inthe form of free compounds like a free base or add.

Any compound that is a solvate of a compound according to the inventionlike a compound according to general formula I defined above isunderstood to be also covered by the scope of the invention. Methods ofsolvation are generally known within the art. Suitable solvates arepharmaceutically acceptable solvates. The term “solvate” according tothis invention is to be understood as meaning any form of the activecompound according to the invention in which this compound has attachedto it via non-covalent binding another molecule (most likely a polarsolvent). Especially preferred examples include hydrates andalcoholates, like methanolates or ethanolates.

Any compound that is a prodrug of a compound according to the inventionlike a compound according to general formula I defined above isunderstood to be also covered by the scope of the invention. The term“prodrug” is used in its broadest sense and encompasses thosederivatives that are converted in vivo to the compounds of theinvention. Such derivatives would readily occur to those skilled in theart, and include, depending on the functional groups present in themolecule and without limitation, the following derivatives of thepresent compounds: esters, amino acid esters, phosphate esters, metalsalts sulfonate esters, carbamates, and amides. Examples of well knownmethods of producing a prodrug of a given acting compound are known tothose skilled in the art and can be found e.g. in Krogsgaard-Larsen etal. “Textbook of Drug design and Discovery” Taylor & Francis (April2002).

Any compound that is a N-oxide of a compound according to the inventionlike a compound according to general formula I defined above isunderstood to be also covered by the scope of the invention.

Unless otherwise stated, the compounds of the invention are also meantto include compounds which differ only in the presence of one or moreisotopically enriched atoms. For example, compounds having the presentstructures except for the replacement of a hydrogen by a deuterium ortritium, or the replacement of a carbon by ¹³C- or ¹⁴C-enriched carbonor of a nitrogen by ¹⁵N-enriched nitrogen are within the scope of thisinvention.

The compounds of formula (I) as well as their salts or solvates of thecompounds are preferably in pharmaceutically acceptable or substantiallypure form. By pharmaceutically acceptable form is meant, inter alia,having a pharmaceutically acceptable level of purity excluding normalpharmaceutical additives such as diluents and carriers, and including nomaterial considered toxic at normal dosage levels. Purity levels for thedrug substance are preferably above 50%, more preferably above 70%, mostpreferably above 90%. In a preferred embodiment it is above 95% of thecompound of formula (I), or of its salts. This applies also to itssolvates or prodrugs.

In a further embodiment the compound according to the invention ofgeneral Formula (I)

is a compound wherein

m is 1, 2, 3, 4 or 5;

n is 0, 1, 2, 3, 4 or 5;

p is 0, 1 or 2;

X is a bond, —C(R_(x)R_(x′))—, —O—, —C(O)—, —C(O)NR₇—, —NR₇C(O)— or—C(O)O—;

-   -   wherein R_(x) is selected from halogen, —OR₇, substituted or        unsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆        alkenyl and substituted or unsubstituted C₂₋₆ alkynyl;    -   R_(x′) is selected from hydrogen, halogen, substituted or        unsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆        alkenyl and substituted or unsubstituted C₂₋₆ alkynyl;    -   R₇ is selected from hydrogen, substituted or unsubstituted C₁₋₆        alkyl, substituted or unsubstituted C₂₋₆ alkenyl and substituted        or unsubstituted C₂₋₆ alkynyl;

Y is —CH₂— or —C(O)—;

R_(1′) is selected from substituted or unsubstituted C₁₋₆ alkyl,substituted or unsubstituted C₂₋₆ alkenyl, substituted or unsubstitutedC₂₋₆ alkynyl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted aryl and substituted or unsubstituted heterocyclyl;

-   -   wherein said cycloalkyl, aryl or heterocyclyl in R_(1′) if        substituted, is substituted with one or more substituent/s        selected from halogen, —R₁₁, —OR₁₁, —NO₂, —NR₁₁R_(11′″),        NR₁₁C(O)R_(11′), —NR₁₁S(O)₂R_(11′), —S(O)₂NR₁₁R_(11′),        —NR₁₁C(O)NR_(11′)R_(11″), —SR₁₁, —S(O)R₁₁, S(O)₂R₁₁, —CN,        haloalkyl, haloalkoxy, —C(O)OR₁₁, —C(O)NR₁₁R_(11′), —OCH₂CH₂OH,        —NR₁₁S(O)₂NR_(11′)R_(11″) and C(CH₃)₂OR₁₁;    -   additionally, cycloalkyl or non-aromatic heterocyclyl in R_(1′),        if substituted, may also be substituted with

-   -   wherein the alkyl, alkenyl or alkynyl in R_(1′), if substituted,        is substituted with one or more substituent/s selected from        —OR₁₁, halogen, —CN, haloalkyl, haloalkoxy and —NR₁₁R_(11′″);    -   wherein R₁₁, R_(11′) and R_(11″) are independently selected from        hydrogen, unsubstituted C₁₋₆ alkyl, unsubstituted C₂₋₆ alkenyl        and unsubstituted C₂₋₆ alkynyl;    -   and wherein R_(11′″) is selected from hydrogen, unsubstituted        C₁₋₆ alkyl, unsubstituted C₂₋₆ alkenyl, unsubstituted C₂₋₆        alkynyl and -Boc;

R₂ is selected from hydrogen, substituted or unsubstituted C₁₋₆ alkyl,substituted or unsubstituted C₂₋₆ alkenyl, substituted or unsubstitutedC₂₋₆ alkynyl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted aryl and substituted or unsubstituted heterocyclyl;

-   -   wherein said cycloalkyl, aryl or heterocyclyl in R₂, if        substituted, is substituted with one or more substituent/s        selected from halogen, —R₁₂, —OR₁₂, —NO₂, —NR₁₂R_(12′″),        NR₁₂C(O)R_(12′), —NR₁₂S(O)₂R_(12′), —S(O)₂NR₁₂R_(12′),        —NR₁₂C(O)NR_(12′)R_(12″), —SR₁₂, —S(O)R₁₂, S(O)₂R₁₂, —CN,        haloalkyl, haloalkoxy, —C(O)OR₁₂, —C(O)NR₁₂R_(12′), —OCH₂CH₂OH,        —NR₁₂S(O)₂NR_(12′)R_(12″) and C(CH₃)₂OR₁₂;    -   additionally, cycloalkyl or non-aromatic heterocyclyl in R₂, if        substituted, may also be substituted with

-   -   wherein the alkyl, alkenyl or alkynyl in R₂, if substituted, is        substituted with one or more substituent/s selected from —OR₁₂,        halogen, —CN, haloalkyl, haloalkoxy and —NR₁₂R_(12′″);    -   wherein R₁₂, R_(12′) and R_(12″) are independently selected from        hydrogen, unsubstituted C₁₋₆ alkyl, unsubstituted C₂₋₆ alkenyl        and unsubstituted C₂₋₆ alkynyl;    -   and wherein R_(12′″) is selected from hydrogen, unsubstituted        C₁₋₆ alkyl, unsubstituted C₂₋₆ alkenyl, unsubstituted C₂₋₆        alkynyl and -Boc;

R₃ and R_(3′) are independently selected from hydrogen, substituted orunsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl,substituted or unsubstituted C₂₋₆ alkynyl, substituted or unsubstitutedcycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted orunsubstituted alkylaryl, substituted or unsubstituted aryl, substitutedor unsubstituted heterocyclyl or substituted or unsubstitutedalkylheterocyclyl;

alternatively R₃ and R_(3′) taken together with the connecting C-atommay form an substituted or unsubstituted cycloalkyl;

R₄ and R_(4′) are independently selected from hydrogen, substituted orunsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl andsubstituted or unsubstituted C₂₋₆ alkynyl;

R₅ and R_(5′) are independently selected from hydrogen, substituted orunsubstituted C₂₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl,substituted or unsubstituted C₂₋₆ alkynyl, substituted or unsubstitutedcycloalkyl and substituted or unsubstituted heterocyclyl;

alternatively, R₅ and R_(5′) taken together with the connecting C-atommay form an substituted or unsubstituted cycloalkyl or a substituted orunsubstituted heterocyclyl;

R₆ and R_(6′) are independently selected from hydrogen, halogen,substituted or unsubstituted C₁₋₆ alkyl, substituted or unsubstitutedC₂₋₆ alkenyl, substituted or unsubstituted C₂₋₆ alkynyl, —CHOR₈ and—C(O)OR₈;

-   -   wherein R₈ is selected from hydrogen, substituted or        unsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆        alkenyl and substituted or unsubstituted C₂₋₆ alkynyl;

R_(n) is selected from hydrogen, unsubstituted C₁₋₆ alkyl, unsubstitutedC₂₋₆ alkenyl and unsubstituted C₂₋₆ alkynyl;

the alkyl, alkenyl or alkynyl, other than those defined in R_(1′) or R₂,if substituted, is substituted with one or more substituent/s selectedfrom —OR₁₃, halogen, —CN, haloalkyl, haloalkoxy and —NR₁₃R_(13′″);

-   -   wherein R₁₃ is selected from hydrogen, unsubstituted C₂₋₆ alkyl,        unsubstituted C₂₋₆ alkenyl, and unsubstituted C₂₋₆ alkynyl;    -   R_(13′″) is selected from hydrogen, unsubstituted C₁₋₆ alkyl,        unsubstituted C₂₋₆ alkenyl, unsubstituted C₂₋₆ alkynyl and -Boc;

the aryl, heterocyclyl or cycloalkyl other than those defined in R_(1′)or R₂, if substituted, is substituted with one or more substituent/sselected from halogen, —R₁₄, —OR₁₄, —NO₂, —NR₁₄R_(14′″),NR₁₄C(O)R_(14′), —NR₁₄S(O)₂R_(14′), —S(O)₂NR₁₄R_(14′),—NR₁₄C(O)NR_(14′)R_(14″), —SR₁₄, —S(O)R₁₄, S(O)₂R₁₄, —CN, haloalkyl,haloalkoxy, —C(O)OR₁₄, —C(O)NR₁₄R_(14′), —OCH₂CH₂OH,—NR₁₄S(O)₂NR_(14′)R_(14″) and C(CH₃)₂OR₁₄;

additionally, wherein cycloalkyl or non-aromatic heterocyclyl, otherthan those defined in R_(1′) or R₂, if substituted, may also besubstituted with

-   -   wherein R₁₄, R_(14′) and R_(14″) are independently selected from        hydrogen, unsubstituted C₁₋₆ alkyl, unsubstituted C₂₋₆ alkenyl,        unsubstituted C₂₋₆ alkynyl, unsubstituted aryl, unsubstituted        cycloalkyl and unsubstituted heterocyclyl;    -   and wherein R_(14′″) is selected from hydrogen, unsubstituted        C₁₋₆ alkyl, unsubstituted C₂₋₆ alkenyl, unsubstituted C₂₋₆        alkynyl and -Boc;

These preferred compounds according to the invention are optionally inform of one of the stereoisomers, preferably enantiomers ordiastereomers, a racemate or in form of a mixture of at least two of thestereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In a further embodiment the compound according to the invention ofgeneral Formula (I) is a compound wherein

m is 1, 2, 3, 4 or 5;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In a further embodiment the compound according to the invention ofgeneral Formula (I) is a compound wherein

n is 0, 1, 2, 3, 4 or 5;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In a further embodiment the compound according to the invention ofgeneral f Formula (I) is a compound wherein

p is 0, 1 or 2;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In a further embodiment the compound according to the invention ofgeneral Formula (I) is a compound wherein

X is a bond, —C(R_(x)R_(x′)), —O—, —C(O)—, —C(O)NR₇—, —NR₇C(O)— or—C(O)O—;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

X is a bond;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

X is —C(R_(x)R_(x′))—;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

X is —O—;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

X is C═O;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

X is —C(O)NR₇—;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

X is —NR₇C(O)—;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

X is —C(O)O—;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In a further embodiment the compound according to the invention ofgeneral Formula (I) is a compound wherein

Y is —CH₂— or —C(O)—;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In a further embodiment the compound according to the invention ofgeneral Formula (I) is a compound wherein

Y is —CH₂—;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In a further embodiment the compound according to the invention ofgeneral Formula (I) is a compound wherein

Y is-C(O)—;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In a further embodiment the compound according to the invention ofgeneral Formula (I) is a compound wherein

R_(1′) is selected from substituted or unsubstituted C₁₋₆ alkyl,substituted or unsubstituted C₂₋₆ alkenyl, substituted or unsubstitutedC₂₋₆ alkynyl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted aryl and substituted or unsubstituted heterocyclyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In a further embodiment the compound according to the invention ofgeneral Formula (I) is a compound wherein

R_(1′) is selected from substituted or unsubstituted C₁₋₆ alkyl,substituted or unsubstituted C₂₋₆ alkenyl, substituted or unsubstitutedC₂₋₆ alkynyl and substituted or unsubstituted aryl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In a further embodiment the compound according to the invention ofgeneral Formula (I) is a compound wherein

R_(1′) is selected from substituted or unsubstituted C₁₋₆ alkyl andsubstituted or unsubstituted aryl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In a further embodiment the compound according to the invention ofgeneral Formula (I) is a compound wherein

R₂ is selected from hydrogen, substituted or unsubstituted C₁₋₆ alkyl,substituted or unsubstituted C₂₋₆ alkenyl, substituted or unsubstitutedC₂₋₆ alkynyl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted aryl and substituted or unsubstituted heterocyclyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In a further embodiment the compound according to the invention ofgeneral Formula (I) is a compound wherein

R₂ is selected from hydrogen, substituted or unsubstituted C₁₋₆ alkyl,substituted or unsubstituted C₂₋₆ alkenyl, substituted or unsubstitutedC₂₋₆ alkynyl and substituted or unsubstituted aryl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In a further embodiment the compound according to the invention ofgeneral Formula (I) is a compound wherein

R₂ is selected from hydrogen, substituted or unsubstituted C₁₋₆ alkyl,and substituted or unsubstituted aryl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theaccording to the invention of general Formula (I) is a compound wherein

R₃ and R_(3′) are independently selected from hydrogen, substituted orunsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl,substituted or unsubstituted C₂₋₆ alkynyl, substituted or unsubstitutedcycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted orunsubstituted alkylaryl, substituted or unsubstituted aryl, substitutedor unsubstituted heterocyclyl or substituted or unsubstitutedalkylheterocyclyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theaccording to the invention of general Formula (I) is a compound wherein

R₃ and R_(3′) are independently selected from hydrogen, substituted orunsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl,substituted or unsubstituted C₂₋₆ alkynyl, substituted or unsubstitutedcycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted orunsubstituted alkylaryl, substituted or unsubstituted aryl, substitutedor unsubstituted heterocyclyl or substituted or unsubstitutedalkylheterocyclyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theaccording to the invention of general Formula (I) is a compound wherein

R₃ and R_(3′) are independently selected from hydrogen, substituted orunsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl andsubstituted or unsubstituted C₂₋₆ alkynyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theaccording to the invention of general Formula (I) is a compound wherein

R₃ and R_(3′) are independently selected from hydrogen and substitutedor unsubstituted C₁₋₆ alkyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theaccording to the invention of general Formula (I) is a compound wherein

R₃ and R_(3′) taken together with the connecting C-atom may form ansubstituted or unsubstituted cycloalkyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

R₄ and R_(4′) are independently selected from hydrogen, substituted orunsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl andsubstituted or unsubstituted C₂₋₆ alkynyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

R₅ and R_(5′) are independently selected from hydrogen, substituted orunsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl andsubstituted or unsubstituted C₂₋₆ alkynyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

R₅ and R_(5′) are independently selected from hydrogen and substitutedor unsubstituted C₁₋₆ alkyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

R₅ and R_(5′) taken together with the connecting C-atom may form ansubstituted or unsubstituted cycloalkyl or a substituted orunsubstituted heterocyclyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of die compound according to theinvention of general Formula (I) is a compound wherein

R₅ and R_(5′) taken together with the connecting C-atom may form ansubstituted or unsubstituted cycloalkyl or a substituted orunsubstituted heterocyclyl, m is 1, X is a bond, n is 0 and R₂ ishydrogen;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

R₅ and R_(5′) taken together with the connecting C-atom may form ansubstituted or unsubstituted cycloalkyl or a substituted orunsubstituted non-aromatic heterocyclyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

R₅ and R_(5′) taken together with the connecting C-atom may form ansubstituted or unsubstituted cycloalkyl or a substituted orunsubstituted non-aromatic heterocyclyl, m is 1, X is a bond, n is 0 andR₂ is hydrogen;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

R₆ and R_(6′) are independently selected from hydrogen, halogen,substituted or unsubstituted C₁₋₆ alkyl, substituted or unsubstitutedC₂₋₆ alkenyl, substituted or unsubstituted C₂₋₆ alkynyl, —CHOR₈ and—C(O)OR₈;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

R₆ and R_(6′) are independently selected from hydrogen, substituted orunsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl andsubstituted or unsubstituted C₂₋₆ alkynyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

R₆ and R_(6′) are independently selected from hydrogen and substitutedor unsubstituted C₁₋₆ alkyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

R₇ is selected from hydrogen, substituted or unsubstituted C₁₋₆ alkyl,substituted or unsubstituted C₂₋₆ alkenyl and substituted orunsubstituted C₂₋₆ alkynyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

R₈ is selected from hydrogen, substituted or unsubstituted C₁₋₆ alkyl,substituted or unsubstituted C₂₋₆ alkenyl and substituted orunsubstituted alkynyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

R₁₁, R_(11′) and R_(11″) are independently selected from hydrogen,unsubstituted C₁₋₆ alkyl, unsubstituted C₂₋₆ alkenyl and unsubstitutedC₂₋₆ alkynyl;

and wherein R_(11′″) is selected from hydrogen, unsubstituted C₁₋₆alkyl, unsubstituted C₂₋₆ alkenyl, unsubstituted C₂₋₆ alkynyl and -Boc;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

R₁₁, R_(11′) and R_(11″) are independently selected from hydrogen,unsubstituted C₁₋₆ alkyl, unsubstituted C₂₋₆ alkenyl and unsubstitutedC₂₋₆ alkynyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

R_(11′″) is selected from hydrogen, unsubstituted C₁₋₆ alkyl,unsubstituted C₂₋₆ alkenyl, unsubstituted C₂₋₆ alkynyl and -Boc;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

R₁₂, R_(12′) and R_(12″) are independently selected from hydrogen,unsubstituted C₂₋₆ alkyl, unsubstituted C₂₋₆ alkenyl and unsubstitutedC₂₋₆ alkynyl;

and wherein R_(12′″) is selected from hydrogen, unsubstituted C₁₋₆alkyl, unsubstituted C₂₋₆ alkenyl, unsubstituted C₂₋₆ alkynyl and -Boc;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

R₁₂, R_(12′) and R_(12″) are independently selected from hydrogen,unsubstituted C₁₋₆ alkyl, unsubstituted C₂₋₆ alkenyl and unsubstitutedC₂₋₆ alkynyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

R_(12′″) is selected from hydrogen, unsubstituted C₁₋₆ alkyl,unsubstituted C₂₋₆ alkenyl, unsubstituted C₂₋₆ alkynyl and -Boc;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

R₁₃ is selected from hydrogen, unsubstituted C₁₋₆ alkyl, unsubstitutedC₂₋₆ alkenyl, and unsubstituted C₂₋₆ alkynyl;

R_(13′″) is selected from hydrogen, unsubstituted C₁₋₆ alkyl,unsubstituted C₂₋₆ alkenyl, unsubstituted C₂₋₆ alkynyl and -Boc;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

R₁₃ is selected from hydrogen, unsubstituted C₁₋₆ alkyl, unsubstitutedC₂₋₆ alkenyl, and unsubstituted C₂₋₆ alkynyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

R_(13′″) is selected from hydrogen, unsubstituted C₁₋₆ alkyl,unsubstituted C₂₋₆ alkenyl, unsubstituted C₂₋₆ alkynyl and -Boc;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

R₁₄, R_(14′) and R_(14″) are independently selected from hydrogen,unsubstituted C₁₋₆ alkyl, unsubstituted C₂₋₆ alkenyl, unsubstituted C₂₋₆alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstitutedheterocyclyl;

and wherein R_(14′″) is selected from hydrogen, unsubstituted C₁₋₆alkyl, unsubstituted C₂₋₆ alkenyl, unsubstituted C₂₋₆ alkynyl and -Boc;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

R₁₄, R_(14′) and R_(14″) are independently selected from hydrogen,unsubstituted C₁₋₆ alkyl, unsubstituted C₂₋₆ alkenyl, unsubstituted C₂₋₆alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstitutedheterocyclyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

R_(14′″) is selected from hydrogen, unsubstituted C₁₋₆ alkyl,unsubstituted C₂₋₆ alkenyl, unsubstituted C₂₋₆ alkynyl and -Boc;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

R_(x) is selected from halogen, —OR₇, substituted or unsubstituted C₁₋₆alkyl, substituted or unsubstituted C₂₋₆ alkenyl and substituted orunsubstituted C₂₋₆ alkynyl;

R_(x′) is selected from hydrogen, halogen, substituted or unsubstitutedC₁₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl and substituted orunsubstituted C₂₋₆ alkynyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

R_(x) is selected from halogen, —OR₇, substituted or unsubstituted C₁₋₆alkyl, substituted or unsubstituted C₂₋₆ alkenyl and substituted orunsubstituted C₂₋₆ alkynyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

R_(x′) is selected from hydrogen, halogen, substituted or unsubstitutedC₁₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl and substituted orunsubstituted C₂₋₆ alkynyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

R_(n) is selected from hydrogen, unsubstituted C₁₋₆ alkyl, unsubstitutedC₂₋₆ alkenyl and unsubstituted C₂₋₆ alkynyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I) is a compound wherein

R_(n) is selected from hydrogen and unsubstituted C₁₋₆ alkyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the compound according to theinvention of general Formula (I), is a compound wherein

m is 1, 2, 3, 4 or 5;

n is 0, 1, 2, 3, 4 or 5;

p is 0, 1 or 2;

Y is —CH₂— or —C(O)—;

X is a bond, —C(R_(x)R_(x′))—, —O—, —C(O)—, —C(O)NR₇, —NR₇C(O)— or—C(O)O—;

R_(1′) is selected from substituted or unsubstituted C₁₋₆ alkyl,substituted or unsubstituted C₂₋₆ alkenyl, substituted or unsubstitutedC₂₋₆ alkynyl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted aryl and substituted or unsubstituted heterocyclyl;

wherein

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl; more preferably the C₁₋₆alkyl is methyl or ethyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

and/or

the aryl is selected from phenyl, naphtyl, or anthracene; preferably isnapthyl or phenyl; more preferably is phenyl;

and/or

the heterocyclyl is a heterocyclic ring system of one or more saturatedor unsaturated rings of which at least one ring contains one or moreheteroatoms from the group consisting of nitrogen, oxygen and/or sulfurin the ring; preferably is a heterocyclic ring system of one or twosaturated or unsaturated rings of which at least one ring contains oneor more heteroatoms from the group consisting of nitrogen, oxygen and/orsulfur in the ring, more preferably is selected from imidazole,oxadiazole, tetrazole, pyridine, pyrimidine, piperidine, piperazine,benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole,thiazole, benzothiazole, tetrahydropyrane, morpholine, indoline, furan,triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole,pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine,benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazoleoxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole andquinazoline;

and/or

the cycloalkyl is C₃₋₈ cycloalkyl like cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C₃₋₇cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, orcycloheptyl; more preferably from C₃₋₆ cycloalkyl like cyclopropyl,cyclobutyl, cyclopentyl or cyclohexyl;

-   -   and/or

R₂ is selected from hydrogen, substituted or unsubstituted C₁₋₆ alkyl,substituted or unsubstituted C₂₋₆ alkenyl, substituted or unsubstitutedC₂₋₆ alkynyl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted aryl and substituted or unsubstituted heterocyclyl;

wherein

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl; more preferably the C₁₋₆alkyl is isopropyl or isobutyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

and/or

the aryl is selected from phenyl, naphtyl, or anthracene; preferably isnapthyl or phenyl; more preferably is phenyl;

and/or

the heterocyclyl is a heterocyclic ring system of one or more saturatedor unsaturated rings of which at least one ring contains one or moreheteroatoms from the group consisting of nitrogen, oxygen and/or sulfurin the ring; preferably is a heterocyclic ring system of one or twosaturated or unsaturated rings of which at least one ring contains oneor more heteroatoms from the group consisting of nitrogen, oxygen and/orsulfur in the ring, more preferably is selected from imidazole,oxadiazole, tetrazole, pyridine, pyrimidine, piperidine, piperazine,benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole,thiazole, benzothiazole, tetrahydropyrane, morpholine, indoline, furan,triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole,pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine,benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazoleoxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole andquinazoline;

and/or

the cycloalkyl is C₂₋₆ cycloalkyl like cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C₃₋₇cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, orcycloheptyl; more preferably from C₃₋₆ cycloalkyl like cyclopropyl,cyclobutyl, cyclopentyl or cyclohexyl;

-   -   and/or

R₃ and R_(3′) are independently selected from hydrogen, substituted orunsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl,substituted or unsubstituted C₂₋₆ alkynyl, substituted or unsubstitutedcycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted orunsubstituted alkylaryl, substituted or unsubstituted aryl, substitutedor unsubstituted heterocyclyl or substituted or unsubstitutedalkylheterocyclyl;

-   -   wherein

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methyl propyl; preferably the C₁₋₆ alkylis methyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

and/or

the aryl is selected from phenyl, naphtyl, or anthracene; preferably isnapthyl or phenyl;

and/or

the heterocyclyl is a heterocyclic ring system of one or more saturatedor unsaturated rings of which at least one ring contains one or moreheteroatoms from the group consisting of nitrogen, oxygen and/or sulfurin the ring; preferably is a heterocyclic ring system of one or twosaturated or unsaturated rings of which at least one ring contains oneor more heteroatoms from the group consisting of nitrogen, oxygen and/orsulfur in the ring, more preferably is selected from imidazole,oxadiazole, tetrazole, pyridine, pyrimidine, piperidine, piperazine,benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole,thiazole, benzothiazole, tetrahydropyrane, morpholine, indoline, furan,triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole,pyrazine, pyrrolo>[2,3b]pyridine, quinoline, isoquinoline, phthalazine,benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazoleoxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole andquinazoline;

and/or

the cycloalkyl is C₃₋₆ cycloalkyl like cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C₃₋₇cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, orcycloheptyl; more preferably from C₃₋₆ cycloalkyl like cyclopropyl,cyclobutyl, cyclopentyl or cyclohexyl;

and/or

R₃ and R_(3′) taken together with the connecting C-atom may form ansubstituted or unsubstituted cycloalkyl;

-   -   wherein

the cycloalkyl is C₃₋₈ cycloalkyl like cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C₃₋₇cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, orcycloheptyl; more preferably from C₃₋₆ cycloalkyl like cyclopropyl,cyclobutyl, cyclopentyl or cyclohexyl; more preferably the cycloalkyl iscyclopropyl;

and/or

R₄ and R_(4′) are independently selected from hydrogen, substituted orunsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl andsubstituted or unsubstituted C₂₋₆ alkynyl;

wherein

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

and/or

R₅ and R_(5′) are independently selected from hydrogen, substituted orunsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl andsubstituted or unsubstituted C₂₋₆ alkynyl;

-   -   alternatively, R₅ and R_(5′) taken together with the connecting        C-atom may form an substituted or unsubstituted cycloalkyl or a        substituted or unsubstituted heterocyclyl;

wherein

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl; more preferably the C₁₋₆alkyl is methyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

and/or

the heterocyclyl is a heterocyclic ring system of one or more saturatedor unsaturated rings of which at least one ring contains one or moreheteroatoms from the group consisting of nitrogen, oxygen and/or sulfurin the ring; preferably is a heterocyclic ring system of one or twosaturated or unsaturated rings of which at least one ring contains oneor more heteroatoms from the group consisting of nitrogen, oxygen and/orsulfur in the ring, more preferably is selected from imidazole,oxadiazole, tetrazole, pyridine, pyrimidine, piperidine, piperazine,benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole,thiazole, benzothiazole, tetrahydropyrane, morpholine, indoline, furan,triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole,pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine,benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazoleoxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole andquinazoline; preferably, the heterocyclyl is non-aromatic heterocyclyl;

and/or

the cycloalkyl is C₃₋₈ cycloalkyl like cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C₃₋₇cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, orcycloheptyl; more preferably from C₃₋₆ cycloalkyl like cyclopropyl,cyclobutyl, cyclopentyl or cyclohexyl;

and/or

R₆ and R_(6′) are independently selected from hydrogen, halogen,substituted or unsubstituted C₁₋₆ alkyl, substituted or unsubstitutedC₂₋₆ alkenyl, substituted or unsubstituted C₂₋₆ alkynyl, —CHOR₈ and—C(O)OR₈;

wherein

the C₂₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl; more preferably the C₁₋₆alkyl is methyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

and/or

R₇ is selected from hydrogen, substituted or unsubstituted C₁₋₆ alkyl,substituted or unsubstituted C₂₋₆ alkenyl and substituted orunsubstituted C₂₋₆ alkynyl;

wherein

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

and/or

R₈ is selected from hydrogen, substituted or unsubstituted C₁₋₆ alkyl,substituted or unsubstituted C₂₋₆ alkenyl and substituted orunsubstituted C₂₋₆ alkynyl;

wherein

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

and/or

R₁₁, R_(11′) and R_(11″) are independently selected from hydrogen,unsubstituted C₁₋₆ alkyl, unsubstituted C₂₋₆ alkenyl and unsubstitutedC₂₋₆ alkynyl;

and wherein R_(11′″) is selected from hydrogen, unsubstituted C₁₋₆alkyl, unsubstituted C₂₋₆ alkenyl, unsubstituted C₂₋₆ alkynyl and -Boc;

wherein

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

and/or

R₁₂, R_(12′) and R_(12′″) are independently selected from hydrogen,unsubstituted C₁₋₆ alkyl, unsubstituted C₂₋₆ alkenyl and unsubstitutedC₂₋₆ alkynyl;

and wherein R_(12′″) is selected from hydrogen, unsubstituted C₁₋₆alkyl, unsubstituted C₂₋₆ alkenyl, unsubstituted C₂₋₆ alkynyl and -Boc;

wherein

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

and/or

R₁₃ is selected from hydrogen, unsubstituted C₁₋₆ alkyl, unsubstitutedC₂₋₆ alkenyl, and unsubstituted C₂₋₆ alkynyl;

R_(13′″) is selected from hydrogen, unsubstituted C₁₋₆ alkyl,unsubstituted C₂₋₆ alkenyl, unsubstituted C₂₋₆ alkynyl and -Boc;

wherein

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

and/or R₁₄, R_(14′) and R_(14′″) are independently selected fromhydrogen, unsubstituted C₁₋₆ alkyl, unsubstituted C₂₋₆ alkenyl,unsubstituted C₂₋₆ alkynyl, unsubstituted aryl, unsubstituted cycloalkyland unsubstituted heterocyclyl;

and wherein R_(14′″) is selected from hydrogen, unsubstituted C₁₋₆alkyl, unsubstituted C₂₋₆ alkenyl, unsubstituted C₂₋₆ alkynyl and -Boc;

wherein

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

and/or

the aryl is selected from phenyl, naphtyl and anthracene; preferably isnapthyl or phenyl;

and/or

the heterocyclyl is a heterocyclic ring system of one or more saturatedor unsaturated rings of which at least one ring contains one or moreheteroatoms from the group consisting of nitrogen, oxygen and/or sulfurin the ring; preferably is a heterocyclic ring system of one or twosaturated or unsaturated rings of which at least one ring contains oneor more heteroatoms from the group consisting of nitrogen, oxygen and/orsulfur in the ring, more preferably is selected from imidazole,oxadiazole, tetrazole, pyridine, pyrimidine, piperidine, piperazine,benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole,thiazole, benzothiazole, tetrahydropyrane, morpholine, indoline, furan,triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole,pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine,benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazoleoxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole andquinazoline;

and/or

the cycloalkyl is C₃₋₈ cycloalkyl like cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C₃₋₇cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, orcycloheptyl; more preferably from C₃₋₆ cycloalkyl like cyclopropyl,cyclobutyl, cyclopentyl or cyclohexyl;

and/or

R_(x) is selected from halogen, —OR₇, substituted or unsubstituted C₁₋₆alkyl, substituted or unsubstituted C₂₋₆ alkenyl and substituted orunsubstituted C₂₋₆ alkynyl;

wherein

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

and/or

R_(x′) is selected from hydrogen, halogen, substituted or unsubstitutedC₁₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl and substituted orunsubstituted C₂₋₆ alkynyl;

wherein

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

and/or

R_(n) is selected from hydrogen, unsubstituted C₁₋₆ alkyl, unsubstitutedC₂₋₆ alkenyl and unsubstituted C₂₋₆ alkynyl;

wherein

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl, preferably the C₁₋₆ alkylis methyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein in R_(1′) as defined inany of the embodiments of the present invention,

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl; more preferably the C₁₋₆alkyl is methyl or ethyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

and/or

the aryl is selected from phenyl, naphtyl, or anthracene; preferably isnapthyl or phenyl; more preferably is phenyl;

and/or

the heterocyclyl is a heterocyclic ring system of one or more saturatedor unsaturated rings of which at least one ring contains one or moreheteroatoms from the group consisting of nitrogen, oxygen and/or sulfurin the ring; preferably is a heterocyclic ring system of one or twosaturated or unsaturated rings of which at least one ring contains oneor more heteroatoms from the group consisting of nitrogen, oxygen and/orsulfur in the ring, more preferably is selected from imidazole,oxadiazole, tetrazole, pyridine, pyrimidine, piperidine, piperazine,benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole,thiazole, benzothiazole, tetrahydropyrane, morpholine, indoline, furan,triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole,pyrazine, pyrrolo[2.3b]pyridine, quinoline, isoquinoline, phthalazine,benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazoleoxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole andquinazoline;

and/or

the cycloalkyl is C₃₋₈ cycloalkyl like cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C₃₋₇cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, orcycloheptyl; more preferably from C₂₋₆ cycloalkyl like cyclopropyl,cyclobutyl, cyclopentyl or cyclohexyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein in R₂ as defined in anyof the embodiments of the present invention, the C₁₋₆ alkyl ispreferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl,isopropyl and 2-methyl propyl; more preferably the C₁₋₆ alkyl isisopropyl or isobutyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

and/or

the aryl is selected from phenyl, naphtyl, or anthracene; preferably isnapthyl or phenyl; more preferably is phenyl;

and/or

the heterocyclyl is a heterocyclic ring system of one or more saturatedor unsaturated rings of which at least one ring contains one or moreheteroatoms from the group consisting of nitrogen, oxygen and/or sulfurin the ring; preferably is a heterocyclic ring system of one or twosaturated or unsaturated rings of which at least one ring contains oneor more heteroatoms from the group consisting of nitrogen, oxygen and/orsulfur in the ring, more preferably is selected from imidazole,oxadiazole, tetrazole, pyridine, pyrimidine, piperidine, piperazine,benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole,thiazole, benzothiazole, tetrahydropyrane, morpholine, indoline, furan,triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole,pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine,benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazoleoxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole andquinazoline;

and/or

the cycloalkyl is C₃₋₈ cycloalkyl like cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C₃₋₇cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, orcycloheptyl; more preferably from C₃₋₆ cycloalkyl like cyclopropyl,cyclobutyl, cyclopentyl or cyclohexyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein in R₃ and R_(3′) asdefined in any of the embodiments of the present invention,

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

and/or

the aryl is selected from phenyl, naphtyl, or anthracene; preferably isnapthyl or phenyl;

and/or

the heterocyclyl is a heterocyclic ring system of one or more saturatedor unsaturated rings of which at least one ring contains one or moreheteroatoms from the group consisting of nitrogen, oxygen and/or sulfurin the ring; preferably is a heterocyclic ring system of one or twosaturated or unsaturated rings of which at least one ring contains oneor more heteroatoms from the group consisting of nitrogen, oxygen and/orsulfur in the ring, more preferably is selected from imidazole,oxadiazole, tetrazole, pyridine, pyrimidine, piperidine, piperazine,benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole,thiazole, benzothiazole, tetrahydropyrane, morpholine, indoline, furan,triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole,pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine,benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazoleoxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole andquinazoline;

and/or

the cycloalkyl is C₃₋₈ cycloalkyl like cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C₃₋₇cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, orcycloheptyl; more preferably from C₃₋₆ cycloalkyl like cyclopropyl,cyclobutyl, cyclopentyl or cyclohexyl; more preferably the cycloalkyl iscyclopropyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein in R₃ and R_(3′) asdefined in any of the embodiments of the present invention,

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl; preferably the C₁₋₆ alkylis methyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

and/or

the aryl is selected from phenyl, naphtyl, or anthracene; preferably isnapthyl or phenyl;

and/or

the heterocyclyl is a heterocyclic ring system of one or more saturatedor unsaturated rings of which at least one ring contains one or moreheteroatoms from the group consisting of nitrogen, oxygen and/or sulfurin the ring; preferably is a heterocyclic ring system of one or twosaturated or unsaturated rings of which at least one ring contains oneor more heteroatoms from the group consisting of nitrogen, oxygen and/orsulfur in the ring, more preferably is selected from imidazole,oxadiazole, tetrazole, pyridine, pyrimidine, piperidine, piperazine,benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole,thiazole, benzothiazole, tetrahydropyrane, morpholine, indoline, furan,triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole,pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine,benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazoleoxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole andquinazoline;

and/or

the cycloalkyl is C₃₋₈ cycloalkyl like cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C₃₋₇cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, orcycloheptyl; more preferably from C₃₋₆ cycloalkyl like cyclopropyl,cyclobutyl, cyclopentyl or cyclohexyl; more preferably the cycloalkyl iscyclopropyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein in R₃ and R_(3′) aremethyl.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein in R₃ and R_(3′) arehydrogen.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein in R₄ and R_(4′) asdefined in any of the embodiments of the present invention,

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

optionally in from of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein in R₅ and R_(5′) asdefined in any of the embodiments of the present invention,

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl; more preferably the alkylis methyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

and/or

the heterocyclyl is a heterocyclic ring system of one or more saturatedor unsaturated rings of which at least one ring contains one or moreheteroatoms from the group consisting of nitrogen, oxygen and/or sulfurin the ring; preferably is a heterocyclic ring system of one or twosaturated or unsaturated rings of which at least one ring contains oneor more heteroatoms from the group consisting of nitrogen, oxygen and/orsulfur in the ring, more preferably is selected from imidazole,oxadiazole, tetrazole, pyridine, pyrimidine, piperidine, piperazine,benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole,thiazole, benzothiazole, tetrahydropyrane, morpholine, indoline, furan,triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole,pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine,benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazoleoxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole andquinazoline;

and/or

the cycloalkyl is C₃₋₈ cycloalkyl like cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C₃₋₇cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, orcycloheptyl; more preferably from C₃₋₆ cycloalkyl like cyclopropyl,cyclobutyl, cyclopentyl or cyclohexyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein in R₆ and R_(6′) asdefined in any of the embodiments of the present invention,

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methyl propyl; more preferably the C₁₋₆alkyl is methyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein in R₇ as defined in anyof the embodiments of the present invention,

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein in R₈ as defined in anyof the embodiments of the present invention,

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein in R₁₁, R_(11′) andR_(11″) as defined in any of the embodiments of the present invention,

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein in R_(11′″) as definedin any of the embodiments of the present invention,

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

optionally in form of one of fee stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to generalFormula (I) fee compound is a compound, wherein in R₁₂, R_(12′) andR_(12″) as defined in any of the embodiments of fee present invention,

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methyl propyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein in R_(12′″) as definedin any of the embodiments of the present invention,

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein in R₁₃ and R_(13′″) asdefined in any of the embodiments of the present invention,

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein in R₁₄, R_(14′) andR_(14″) as defined in any of the embodiments of the present invention,

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

and/or

the aryl is selected from phenyl, naphtyl and anthracene; preferably isnapthyl or phenyl;

and/or

the heterocyclyl is a heterocyclic ring system of one or more saturatedor unsaturated rings of which at least one ring contains one or moreheteroatoms from the group consisting of nitrogen, oxygen and/or sulfurin the ring; preferably is a heterocyclic ring system of one or twosaturated or unsaturated rings of which at least one ring contains oneor more heteroatoms from the group consisting of nitrogen, oxygen and/orsulfur in the ring, more preferably is selected from imidazole,oxadiazole, tetrazole, pyridine, pyrimidine, piperidine, piperazine,benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole,thiazole, benzothiazole, tetrahydropyrane, morpholine, indoline, furan,triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole,pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine,benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazoleoxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole andquinazoline;

and/or

the cycloalkyl is C₃₋₈ cycloalkyl like cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C₃₋₇cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, orcycloheptyl; more preferably from C₃₋₆ cycloalkyl like cyclopropyl,cyclobutyl, cyclopentyl or cyclohexyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein in R_(14′″) as definedin any of the embodiments of the present invention,

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein in R_(n) as defined inany of the embodiments of the present invention,

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methyl propyl, preferably the C₁₋₆ alkylis methyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein in R_(x) as defined inany of the embodiments of the present invention,

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein in R_(x′) as defined inany of the embodiments of the present invention,

the C₁₋₆ alkyl is preferably selected from methyl, ethyl, propyl, butyl,pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

the C₂₋₆-alkenyl is preferably selected from ethylene, propylene,butylene, pentylene and hexylene;

and/or

the C₂₋₆-alkynyl is preferably selected from ethyne, propyne, butyne,pentyne and hexyne;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein

X is a bond;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to any one ofgeneral Formulas (I′), (I^(a′)), (I^(b′)), (I^(2′)), (I^(3′)) or(I^(4′)) the compound is a compound, wherein

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein

n is 0, 1, 2, 3, 4 or 5; preferably n is 0, 1 or 2;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein

m is 1, 2, 3, 4 or 5; preferably m is 1 or 2;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein

p is 0, 1 or 2; preferably p is 0 or 1;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein

X is a bond, —C(R_(x)R_(x′))—, —O—, —C(O)—, —C(O)NR₇, —NR₇C(O)— or—C(O)O—; preferably, X is a bond;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein

Y is —CH₂— or —C(O)—;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In a further preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein

X is a bond, —C(R_(x)R_(x′))—, —O—, —C(O)—, —C(O)NR₇—, —NR₇C(O)— or—C(O)O—; preferably X is a bond and/or

m is 1, 2, 3, 4 or 5; preferably m is 1 or 2; and/or

n is 0, 1, 2, 3, 4 or 5; preferably n is 0; and/or

p is 0, 1 or 2; preferably p is 0;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another preferred embodiment of the invention according to generalFormula (I) the compound is a compound, wherein

m is 1, or 2;

n is 0;

p is 0, or 1;

X is a bond;

Y is —CH₂— or —C(O)—;

R_(1′) is selected from substituted or unsubstituted C₁₋₆ alkyl,substituted or unsubstituted cycloalkyl and substituted or unsubstitutedaryl;

R₂ is selected from hydrogen, substituted or unsubstituted C₁₋₆ alkyl,substituted or unsubstituted aryl and substituted or unsubstitutedheterocyclyl;

R₃ and R_(3′) taken together with the connecting C-atom form ansubstituted or unsubstituted cycloalkyl;

R₄ and R_(4′) are hydrogen;

R₅ and R_(5′) are independently selected from hydrogen and substitutedor unsubstituted C₁₋₆ alkyl;

R_(n) is selected from hydrogen and unsubstituted C₁₋₆ alkyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

Preferably, in this embodiment directly above the following additionallyapplies:

-   -   wherein said aryl in R_(1′) if substituted, is substituted with        one or more substituent/s selected from halogen, —R₁₁, —OR₁₁,        —NO₂, —NR₁₁R_(11′″), NR₁₁C(O)R_(11′), —NR₁₁S(O)₂R_(11′),        —S(O)₂NR₁₁R_(11′), —NR₁₁C(O)NR₁₁R_(11′), —SR₁₁, —S(O)R₁₁,        S(O)₂R₁₁, —CN, haloalkyl, haloalkoxy, —C(O)OR₁₁,        —C(O)NR₁₁R_(11′), —OCH₂CH₂OH, —NR₁₁S(O)₂NR_(11′)R_(11″) and        C(CH₃)₂OR₁₁;    -   wherein the alkyl in R_(1′), if substituted, is substituted with        one or more substituents selected from —OR₁₁, halogen, —CN,        haloalkyl, haloalkoxy and —NR₁₁R_(11′″);    -   wherein R₁₁, R_(11′) and R_(11″) are independently selected from        hydrogen, unsubstituted C₁₋₆ alkyl, unsubstituted C₂₋₆ alkenyl        and unsubstituted C₂₋₆ alkynyl;

and wherein R_(11′″) is selected from hydrogen, unsubstituted C₁₋₆alkyl, unsubstituted C₂₋₆ alkenyl, unsubstituted C₂₋₆ alkynyl and -Boc;

and/or

-   -   wherein said aryl in R₂, if substituted, is substituted with one        or more substituents selected from halogen, —R₁₂, —OR₁₂, —NO₂,        —NR₁₂R_(12′″), NR₁₂C(O)R_(12′), —NR₁₂S(O)₂R_(12′),        —S(O)₂NR₁₂R_(12′), —NR₁₂C(O)NR_(12′)R_(12″), —SR₁₂, —S(O)R₁₂,        S(O)₂R₁₂, —CN, haloalkyl, haloalkoxy, —C(O)OR₁₂,        —C(O)NR₁₂R_(12′), —OCH₂CH₂OH, —NR₁₂S(O)₂NR_(12′)R_(12″) and        C(CH₃)₂OR₁₂;    -   additionally, cycloalkyl or non-aromatic heterocyclyl in R₂, if        substituted, may also be substituted with

-   -   wherein the alkyl in R₂, if substituted, is substituted with one        or more substituents selected from —OR₁₂, halogen, —CN,        haloalkyl, haloalkoxy and —NR₁₂R_(12′″);    -   wherein R₁₂, R_(12′) and R_(12″) are independently selected from        hydrogen, unsubstituted C₁₋₆ alkyl, unsubstituted C₂₋₆ alkenyl        and unsubstituted C₂₋₆ alkynyl;    -   and wherein R_(12′″) is selected from hydrogen, unsubstituted        C₁₋₆ alkyl, unsubstituted C₂₋₆ alkenyl, unsubstituted C₂₋₆        alkynyl and -Boc;

and/or

the alkyl, alkenyl or alkynyl, other than those defined in R_(1′) or R₂,if substituted, is substituted with one or more substituent/s selectedfrom —OR₁₃, halogen, —CN, haloalkyl, haloalkoxy and —NR₁₃R_(13′″);

-   -   wherein R₁₃ is selected from hydrogen, unsubstituted C₁₋₆ alkyl,        unsubstituted C₂₋₆ alkenyl, and unsubstituted C₂₋₆ alkynyl;    -   R_(13′″) is selected from hydrogen, unsubstituted C₁₋₆ alkyl,        unsubstituted C₂₋₆ alkenyl, unsubstituted C₂₋₆ alkynyl and -Boc;

the aryl, heterocyclyl or cycloalkyl other than those defined in R_(1′)or R₂, if substituted, is substituted with one or more substituent/sselected from halogen, —R₁₄, —OR₁₄, —NO₂, —NR₁₄R_(14′″),NR₁₄C(O)R_(14′), —NR₁₄S(O)₂R_(14′), —S(O)₂NR₁₄R_(14′),—NR₁₄C(O)NR_(14′)R_(14″), —SR₁₄, —S(O)R₁₄, S(O)₂R₁₄, —CN, haloalkyl,haloalkoxy, —C(O)OR₁₄, —C(O)NR₁₄R_(14′), —OCH₂CH₂OH,—NR₁₄S(O)₂NR_(14′)R_(14″) and C(CH₃)₂OR₁₄;

additionally, wherein cycloalkyl or non-aromatic heterocyclyl, otherthan those defined in R_(1′) or R₂, if substituted, may also besubstituted with

-   -   wherein R₁₄, R_(14′) and R_(14″) are independently selected from        hydrogen, unsubstituted C₁₋₆ alkyl, unsubstituted C₂₋₆ alkenyl,        unsubstituted C₂₋₆ alkynyl, unsubstituted aryl, unsubstituted        cycloalkyl and unsubstituted heterocyclyl;    -   and wherein R_(14′″) is selected from hydrogen, unsubstituted        C₁₋₆ alkyl, unsubstituted C₂₋₆ alkenyl, unsubstituted C₂₋₆        alkynyl and -Boc;

In another preferred embodiment of the invention according to generalFormula (I), the compound is a compound of Formula (I′)

wherein R₁, R₂, R₃, R_(3′), R₅, R_(5′), R_(n), m and Y are as describedabove or as described below.

In another preferred embodiment of the invention according to generalFormula (I), the compound is a compound of Formula (I′)

m is 1, 2, 3, 4 or 5;

p is 0, 1 or 2;

Y is —CH₂— or —C(O)—;

X is a bond, —C(R_(x)R_(x′))—, —O—, —C(O)—, —C(O)NR₇—, —NR₇C(O)— or—C(O)O—;

-   -   wherein R_(x) is selected from halogen, —OR₇, substituted or        unsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆        alkenyl and substituted or unsubstituted C₂₋₆ alkynyl;

R_(x′) is selected from hydrogen, halogen, substituted or unsubstitutedC₁₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl and substituted orunsubstituted C₂₋₆ alkynyl;

R₇ is selected from hydrogen, substituted or unsubstituted C₁₋₆ alkyl,substituted or unsubstituted C₂₋₆ alkenyl and substituted orunsubstituted C₂₋₆ alkynyl;

R_(1′) is selected from substituted or unsubstituted C₁₋₆ alkyl,substituted or unsubstituted C₂₋₆ alkenyl, substituted or unsubstitutedC₂₋₆ alkynyl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted aryl and substituted or unsubstituted heterocyclyl;

R₂ is selected from hydrogen, substituted or unsubstituted C₁₋₆ alkyl,substituted or unsubstituted C₂₋₆ alkenyl, substituted or unsubstitutedC₂₋₆ alkynyl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted aryl and substituted or unsubstituted heterocyclyl;

R₃ and R_(3′) are independently selected from hydrogen, substituted orunsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl,substituted or unsubstituted C₂₋₆ alkynyl, substituted or unsubstitutedcycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted orunsubstituted alkylaryl, substituted or unsubstituted aryl, substitutedor unsubstituted heterocyclyl or substituted or unsubstitutedalkylheterocyclyl;

alternatively R₃ and R_(3′) taken together with the connecting C-atommay form an substituted or unsubstituted cycloalkyl;

R₄ and R_(4′) are independently selected from hydrogen, substituted orunsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl andsubstituted or unsubstituted C₂₋₆ alkynyl;

R₅ and R_(5′) are independently selected from hydrogen, substituted orunsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl andsubstituted or unsubstituted C₂₋₆ alkynyl;

alternatively, R₅ and R_(5′) taken together with the connecting C-atommay form an substituted or unsubstituted cycloalkyl or a substituted orunsubstituted heterocyclyl;

R_(n) is selected from hydrogen, unsubstituted C₁₋₆ alkyl, unsubstitutedC₂₋₆ alkenyl and unsubstituted C₂₋₆ alkynyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In a further preferred embodiment of the invention according to generalFormula (I) the compound is a compound of Formula (I^(2′)).

wherein R₁, R₂, R₅, R_(5′), R_(n), m and Y are as described above or asdescribed below.

In a further preferred embodiment of the invention according to generalFormula (I) the compound is a compound of Formula (I^(2′)),

m is 1, 2, 3, 4 or 5;

p is 0, 1 or 2;

Y is —CH₂— or —C(O)—;

X is a bond, —C(R_(x)R_(x′))—, —O—, —C(O)—, —C(O)NR₇—, —NR₇C(O)— or—C(O)O—;

-   -   wherein R_(x) is selected from halogen, —OR₇, substituted or        unsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆        alkenyl and substituted or unsubstituted C₂₋₆ alkynyl;    -   R_(x′) is selected from hydrogen, halogen, substituted or        unsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆        alkenyl and substituted or unsubstituted C₂₋₆ alkynyl;    -   R₇ is selected from hydrogen, substituted or unsubstituted C₁₋₆        alkyl, substituted or unsubstituted C₂₋₆ alkenyl and substituted        or unsubstituted C₂₋₆ alkynyl;

R_(1′) is selected from substituted or unsubstituted C₁₋₆ alkyl,substituted or unsubstituted C₂₋₆ alkenyl, substituted or unsubstitutedC₂₋₆ alkynyl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted aryl and substituted or unsubstituted heterocyclyl;

R₂ is selected from hydrogen, substituted or unsubstituted C₁₋₆ alkyl,substituted or unsubstituted C₂₋₆ alkenyl, substituted or unsubstitutedC₂₋₆ alkynyl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted aryl and substituted or unsubstituted heterocyclyl;

R₄ and R_(4′) are independently selected from hydrogen, substituted orunsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl andsubstituted or unsubstituted C₂₋₆ alkynyl;

R₅ and R_(5′) are independently selected from hydrogen, substituted orunsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl andsubstituted or unsubstituted C₂₋₆ alkynyl;

alternatively, R₅ and R_(5′) taken together with the connecting C-atommay form an substituted or unsubstituted cycloalkyl or a substituted orunsubstituted heterocyclyl;

R_(n) is selected from hydrogen, unsubstituted C₁₋₆ alkyl, unsubstitutedC₂₋₆ alkenyl and unsubstituted C₂₋₆ alkynyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In a further preferred embodiment of the invention according to generalFormula (I) the compound is a compound of Formula (I^(3′)),

wherein R_(1′), R₂, R₅, R_(5′), R_(n), m and Y are as described above oras described below.

In a further preferred embodiment of the invention according to generalFormula (I) the compound is a compound of Formula (I^(3′)),

wherein

m is 1, 2, 3, 4 or 5;

p is 0, 1 or 2;

Y is —CH₂— or —C(O)—;

X is a bond, —C(R_(x)R_(x′))—, —O—, —C(O)—, —C(O)NR₇, —NR₇C(O)— or—C(O)O—;

-   -   wherein R_(x) is selected from halogen, —OR₇, substituted or        unsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆        alkenyl and substituted or unsubstituted C₂₋₆ alkynyl;    -   R_(x′) is selected from hydrogen, halogen, substituted or        unsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆        alkenyl and substituted or unsubstituted C₂₋₆ alkynyl;    -   R₇ is selected from hydrogen, substituted or unsubstituted C₁₋₆        alkyl, substituted or unsubstituted C₂₋₆ alkenyl and substituted        or unsubstituted C₂₋₆ alkynyl;

R_(1′) is selected from substituted or unsubstituted C₁₋₆ alkyl,substituted or unsubstituted C₂₋₆ alkenyl, substituted or unsubstitutedC₂₋₆ alkynyl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted aryl and substituted or unsubstituted heterocyclyl;

R₂ is selected from hydrogen, substituted or unsubstituted C₁₋₆ alkyl,substituted or unsubstituted C₂₋₆ alkenyl, substituted or unsubstitutedC₂₋₆ alkynyl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted aryl and substituted or unsubstituted heterocyclyl;

R₄ and R_(4′) are independently selected from hydrogen, substituted orunsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl andsubstituted or unsubstituted C₂₋₆ alkynyl;

R₅ and R_(5′) are independently selected from hydrogen, substituted orunsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl andsubstituted or unsubstituted C₂₋₆ alkynyl;

alternatively, R₅ and R_(5′) taken together with the connecting C-atommay form an substituted or unsubstituted cycloalkyl or a substituted orunsubstituted heterocyclyl;

R_(n) is selected from hydrogen, unsubstituted C₁₋₆ alkyl, unsubstitutedC₂₋₆ alkenyl and unsubstituted C₂₋₆ alkynyl;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In a preferred embodiment

R₁ is a substituted or unsubstituted group selected from ethyl andphenyl.

In a preferred embodiment

R_(1′) is a substituted or unsubstituted group selected from methyl,ethyl and phenyl.

In a preferred embodiment

R₂ is hydrogen or a substituted or unsubstituted group selected fromisopropyl, isobutyl and phenyl; more preferably hydrogen or anunsubstituted group selected from isopropyl, isobutyl and phenyl.

In a preferred embodiment

R₃ and R_(3′) taken together with the connecting C-atom may form asubstituted or unsubstituted cyclopropyl: preferably unsubstitutedcyclopropyl.

In a preferred embodiment

R₃ is substituted or unsubstituted methyl, preferably unsubstitutedmethyl.

In a preferred embodiment

R_(3′) is substituted or unsubstituted methyl, preferably unsubstitutedmethyl.

In a preferred embodiment

R₃ is hydrogen.

In a preferred embodiment

R_(3′) is hydrogen.

In a preferred embodiment

R₃ is substituted or unsubstituted methyl, preferably unsubstitutedmethyl, while R_(3′) is substituted or unsubstituted methyl, preferablyunsubstituted methyl.

In a preferred embodiment

R₃ and R₃ are both substituted or unsubstituted methyl, preferablyunsubstituted methyl.

In a preferred embodiment

R₃ and R₃ are both hydrogen.

In a preferred embodiment

R₄ and R_(4′) are both hydrogen.

In a preferred embodiment

R₅ is hydrogen or substituted or unsubstituted methyl, preferably R₅ ishydrogen or unsubstituted methyl.

In a preferred embodiment

R_(5′) is hydrogen.

In a preferred embodiment

R₅ is hydrogen or substituted or unsubstituted methyl, while R_(5′) ishydrogen, preferably R₅ is hydrogen or unsubstituted methyl, whileR_(5′) is hydrogen.

In a preferred embodiment

R₅ is substituted or unsubstituted methyl, while R_(5′) is hydrogen,preferably R₅ is unsubstituted methyl, while R_(5′) is hydrogen.

In a preferred embodiment

R₅ and R_(5′) are both hydrogen.

In a preferred embodiment

R₆ is hydrogen or substituted or unsubstituted methyl, preferably R₆ ishydrogen or unsubstituted methyl.

In a preferred embodiment

R_(6′) is hydrogen.

In a preferred embodiment

R₆ is hydrogen or substituted or unsubstituted methyl, while R_(6′) ishydrogen, preferably R₆ is hydrogen or unsubstituted methyl, whileR_(6′) is hydrogen.

In a preferred embodiment

R₆ is substituted or unsubstituted methyl, while R_(6′) is hydrogen,preferably R₆ is unsubstituted methyl, while R_(6′) is hydrogen.

In a preferred embodiment

R₆ and R_(6′) are both hydrogen.

In a preferred embodiment

R_(n) is hydrogen or substituted or unsubstituted methyl, preferablyhydrogen or unsubstituted methyl.

In a preferred embodiment

X is a bond.

In a preferred embodiment

Y is —CH₂— or C(O)—;

In another preferred embodiment

n is 0.

In another preferred embodiment

m is 1 or 2;

In another preferred embodiment

p is 0 or 1.

In another preferred embodiment

p is 0.

In an particular embodiment

the halogen is fluorine or chlorine.

In a preferred further embodiment, the compounds of the general Formula(I) are selected from

EX CHEMICAL NAME 1 (5s,8s)-8-(benzylamino)-12-ethyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one 2(5r,8r)-8-(benzylamino)-12-ethyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one 3(5s,8s)-12-ethyl-8[methyl(2-phenylethyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one 4(5r,8r)-12-ethyl-8-[methyl(2-phenylethyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one 5(5s,8s)-8-[benzyl(methyl)amino]-12-ethyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one 6(5s,8s)-12-ethyl-8-[(2-phenylethyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one 7(5r,8r)-12-ethyl-8-[(2-phenylethyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one 8(5s,8s)-8-[benzyl(methyl)amino]-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one 9(5s,8s)-8-(methyl(2-phenylethyl)amino]-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one 10(5s,8s)-8-(benzylamino)-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one 11(5s,8s)-12-phenyl-8-[(2-phenylethyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one 12(5r,8r)-8-(benzylamino)-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one 13(5r,8r)-12-phenyl-8-[(2-phenylethyl)amino-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one 14(5r,8r)-8-[benzyl(methyl)amino]-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one 15(5r,8r)-8-[methyl(2-phenylethyl)amino]-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one 16(5r,8r)-8-[benzyl(methyl)amino]-12-ethyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one 17(5s,8s)-N-benzyl-12-ethyl-N-methyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-8-amine 18(5r,8r)-N-benzyl-12-ethyl-N-methyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-8-amine 19(5s,8s)-N-benzyl-N-methyl-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-8-amine 20(5r,8r)-N-benzyl-N-methyl-12-phenyl-4-oxa-12-azadispiro[2.1.53]tridecan-8-amine 21(5r,8r)-12-ethyl-8-(methylamino)-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one acetate 22(5s,8s)-12-ethyl-8-(methylamino)-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one acetate 23(5s,8s)-8-(methylamino)-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one acetate 24(5r,8r)-8-(methylamino)-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one acetate 25(5s,8s)-N-methyl-12-phenyl-4-oxa-12- azadispiro[2.1.5.3]tridecan-8-amineacetate 26 (5r,8r)-N-rnethyl-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-8-amine acetate 27(5r,8r)-12-ethyl-8-[methyl(3-methylbutyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one 28(5s,8s)-12-ethyl-8-[rnethyl(3-methylbutyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one 29(5s,8s)-8-[methyl(3-methylbutyl)amino]-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one 30(5r,8r)-8-[methyl(3-methylbutyl)amino]-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one 31(5s,8s)-N-methyl-N-(3-methylbutyl)-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-8-amine 32(5r,8r)-N-rnethyl-N-(3-methylbutyl)-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-8-amine 33(5s,8s)-12-ethyl-8-[methyl(2-methylpropyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one 34(5r,8r)-N-methyl-12-phenyl-N-(2-phenylethyl)-4-oxa-12-azadispiro[2.1.5.3]tridecan-8-amine 35(5r,8r)-12-ethyl-N-methyl-N-(3-methylbutyl)-4-oxa-12-azadispiro[2.1.5.3]tridecan-8-amine

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In a preferred further embodiment, the compounds of the general Formula(I) are selected from

EX Structure Chemical name 36

(6s,9s)-9-(benzylamino)-4-ethyl-1-oxa-4- azaspiro[5.5]undecan-3-one 37

(6r,9r)-9-(benzylamino)-4-ethyl-1-oxa-4- azaspiro[5.5]undecan-3-one 38

(6s,9s)-4-ethyl-9-(isobutyl(methyl)amino)-1-oxa-4-azaspiro[5.5]undecan-3-one 39

(6s,9s)-9-(benzylamino)-4-ethyl-2,2-dimethyl-1-oxa-4-azaspiro[5.5]undecan-3-one 40

(6r,9r)-9-(benzylamino)-4-ethyl-2,2-dimethyl-1-oxa-4-azaspiro[5.5]undecan-3-one 41

(6s,9s)-9-(benzyl(methyl)amino)-4-ethyl-1-oxa-4-azaspiro[5.5]undecan-3-one 42

(6r,9r)-9-(benzyl(methyl)amino)-4-ethyl-1-oxa-4-azaspiro[5.5]undecan-3-one 43

(6s,9s)-9-(benzyl(methyl)amino)-4-ethyl-2,2-dimethyl-1-oxa-4-azaspiro[5.5]undecan-3-one 44

(6r,9r)-9-(benzyl(methyl)amino)-4-ethyl-2,2-dimethyl-1-oxa-4-azaspiro[5.5]undecan-3- one 45

((5s,8s)-8-[Benzyl(methyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-12- yl)(phenyl)methanone 46

((5r,8r)-8-[Benzyl(methyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-12- yl)(phenyl)methanone 47

(6s,9s)-4-ethyl-9-(methylamino)-1-oxa-4- azaspiro[5.5]undecan-3-oneacetate 48

(6s,9s)-4-ethyl-2,2-dimethyl-9-(methylamino)-1-oxa-4-azaspiro[5.5]undecan-3-one acetate 49

(6r,9r)-4-ethyl-2,2-dimethyl-9-(methylamino)-1-oxa-4-azaspiro[5.5]undecan-3-one acetate 50

((5s,8s)-8-(methylamino)-4-oxa-12- azadispiro[2.1.5.3]tridecan-12-yl)(phenyl)methanone acetate 51

(6s,9s)-4-ethyl-9-(methyl(phenethyl)amino)-1-oxa-4-azaspiro[5.5]undecan-3-one 52

(6s,9s)-4-ethyl-9-(isopentyl(methyl)amino)-1-oxa-4-azaspiro[5.5]undecan-3-one 53

(6s,9s)-4-ethyl-9-(isopentyl(methyl)amino)-2,2-dimethyl-1-oxa-4-azaspiro[5.5]undecan- 3-one 54

(6s,9s)-4-ethyl-9-(isobutyl(methyl)amino)-2,2-dimethyl-1-oxa-4-azaspiro[5.5]undecan-3- one 55

(6s,9s)-4-ethyl-2,2-dimethyl-9- (methyl(phenethyl)amino)-1-oxa-4-azaspiro[5.5]undecan-3-one 56

(6r,9r)-4-ethyl-2,2-dimethyl-9- (methyl(phenethyl)amino)-1-oxa-4-azaspiro[5.5]undecan-3-one 57

(6r,9r)-4-ethyl-9-(isopentyl(methyl)amino)-2,2-dimethyl-1-oxa-4-azaspiro[5.5]undecan- 3-one 58

((5s,8s)-8-[methyl(phenethyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-12- yl)(phenyl)methanone 59

((5s,8s)-8-[isopentyl(methyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-12- yl)(phenyl)methanone 60

((5s,8s)-8-[isobutyl(methyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-12- yl)(phenyl)methanone 61

(6s,9s)-4-ethyl-N-methyl-N-phenethyl-1-oxa-4-azaspiro[5.5]undecan-9-amine 62

(6s,9s)-N-benzyl-4-ethyl-N,2,2-trimethyl-1-oxa-4-azaspiro[5.5]undecan-9-amine 63

(6s,9s)-4-ethyl-N-isopentyl-N-methyl-1-oxa-4-azaspiro[5.5]undecan-9-amine 64

(6s,9s)-4-ethyl-N-isopentyl-N,2,2-trimethyl-1-oxa-4-azaspiro[5.5]undecan-9-amine 65

(6s,9s)-4-ethyl-N-isobutyl-N,2,2-trimethyl-1-oxa-4-azaspiro[5.5]undecan-9-amine 66

(6s,9s)-4-ethyl-N,2,2-trimethyl-N-phenethyl-1-oxa-4-azaspiro[5.5]undecan-9-amine 67

(5s,8s)-12-benzyl-N-methyl-N-(2- phenylethyl)-4-oxa-12-azadispiro[2.1.5.3]tridecan-8-amine 68

(5s,8s)-12-benzyl-N-isobutyl-N-methyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-8-amine

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In a preferred embodiment of the compound according to the invention ofgeneral Formula (I),

R_(1′) is selected from substituted or unsubstituted C₁₋₆ alkyl,substituted or unsubstituted C₂₋₆ alkenyl, substituted or unsubstitutedC₂₋₆ alkynyl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted aryl and substituted or unsubstituted heterocyclyl;

-   -   wherein said cycloalkyl, aryl or heterocyclyl in R_(1′) if        substituted, is substituted with one or more substituent/s        selected from halogen, —R₁₁, —OR₁₁, —NO₂, —NR₁₁R_(11′),        NR₁₁C(O)R_(11′), —NR₁₁S(O)₂R_(11′), —S(O)₂NR₁₁R_(11′),        —NR₁₁C(O)NR_(11′)R_(11″), —SR₁₁, —S(O)R₁₁, S(O)₂R₁₁, —CN,        haloalkyl, haloalkoxy, —C(O)OR₁₁, —C(O)NR₁₁R_(11′), —OCH₂CH₂OH,        —NR₁₁S(O)₂NR_(11′)R_(11″) and C(CH₃)₂OR₁₁;    -   additionally, cycloalkyl or non-aromatic heterocyclyl in R_(1′)        if substituted, may also be substituted with or

-   -   wherein the alkyl, alkenyl or alkynyl in R_(1′), if substituted,        is substituted with one or more substituent/s selected from        —OR₁₁, halogen, —CN, haloalkyl, haloalkoxy and —NR₁₁R_(11′″);    -   wherein R₁₁, R_(11′) and R_(11″) are independently selected from        hydrogen, unsubstituted C₁₋₆ alkyl, unsubstituted C₂₋₆ alkenyl        and unsubstituted C₂₋₆ alkynyl;    -   and wherein R_(11′″) is selected from hydrogen, unsubstituted        C₁₋₆ alkyl, unsubstituted C₂₋₆ alkenyl, unsubstituted C₂₋₆        alkynyl and -Boc;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another embodiment of the invention the compound of general Formula(I),

R₂ is selected from hydrogen, substituted or unsubstituted C₁₋₆ alkyl,substituted or unsubstituted C₂₋₆ alkenyl, substituted or unsubstitutedC₂₋₆ alkynyl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted aryl and substituted or unsubstituted heterocyclyl;

-   -   wherein said cycloalkyl, aryl or heterocyclyl in R₂, if        substituted, is substituted with one or more substituent/s        selected from halogen, —R₁₂, —OR₁₂, —NO₂, —NR₁₂R_(12′″),        NR₁₂C(O)R_(12′), —NR₁₂S(O)₂R_(12′), —S(O)₂NR₁₂R_(12′),        —NR₁₂C(O)NR_(12′)R_(12″), —SR₁₂, —S(O)R₁₂, —S(O)₂R₁₂, —CN,        haloalkyl, haloalkoxy, —C(O)OR₁₂, —C(O)NR₁₂R_(12′), —OCH₂CH₂OH,        —NR₁₂S(O)₂NR_(12′)R_(12″) and C(CH₃)₂OR₁₂;    -   additionally, cycloalkyl or non-aromatic heterocyclyl in R₂, if        substituted, may also be substituted with

-   -   wherein the alkyl, alkenyl or alkynyl in R₂, if substituted, is        substituted with one or more substituent/s selected from —OR₁₂,        halogen, —CN, haloalkyl, haloalkoxy and —NR₁₂R_(12′″);    -   wherein R₁₂, R_(12′) and R_(12″) are independently selected from        hydrogen, unsubstituted C₁₋₆ alkyl, unsubstituted C₂₋₆ alkenyl        and unsubstituted C₂₋₆ alkynyl;    -   and wherein R_(12′″) is selected from hydrogen, unsubstituted        C₁₋₆ alkyl, unsubstituted C₂₋₆ alkenyl, unsubstituted C₂₋₆        alkynyl and -Boc;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another embodiment of the invention the compound of general Formula(I),

the alkyl, alkenyl or alkynyl, other than those defined in R_(1′) or R₂,if substituted, is substituted with one or more substituent/s selectedfrom —OR₁₃, halogen, —CN, haloalkyl, haloalkoxy and —NR₁₃R_(13′″);

-   -   wherein R₁₃ is selected from hydrogen, unsubstituted C₁₋₆ alkyl,        unsubstituted C₂₋₆ alkenyl, and unsubstituted C₂₋₆ alkynyl;    -   R_(13′″) is selected from hydrogen, unsubstituted C₁₋₆ alkyl,        unsubstituted C₂₋₆ alkenyl, unsubstituted C₂₋₆ alkynyl and -Boc;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another embodiment of the invention the compound of general Formula(I),

the aryl, heterocyclyl or cycloalkyl other than those defined in R_(1′)or R₂, if substituted, is substituted with one or more substituent/sselected from halogen, —R₁₄, —OR₁₄, —NO₂, —NR₁₄R_(14′″),NR₁₄C(O)R_(14′), —NR₁₄S(O)₂R_(14′), —S(O)₂NR₁₄R_(14′),—NR₁₄C(O)NR_(14′)R_(14″), —SR₁₄, —S(O)R₁₄, S(O)₂R₁₄, —CN, haloalkyl,haloalkoxy, —C(O)OR₁₄, —C(O)NR₁₄R_(14′), —OCH₂CH₂OH,—NR₁₄S(O)₂NR_(14′)R_(14″) and C(CH₃)₂OR₁₄;

additionally, wherein cycloalkyl or non-aromatic heterocyclyl, otherthan those defined in R_(1′) or R₂, if substituted, may also besubstituted with

-   -   wherein R₁₄, R_(14′) and R_(14″) are independently selected from        hydrogen, unsubstituted C₁₋₆ alkyl, unsubstituted C₂₋₆ alkenyl,        unsubstituted C₂₋₆ alkynyl, unsubstituted aryl, unsubstituted        cycloalkyl and unsubstituted heterocyclyl;    -   and wherein R_(14′″) is selected from hydrogen, unsubstituted        C₁₋₆ alkyl, unsubstituted C₂₋₆ alkenyl, unsubstituted C₂₋₆        alkynyl and -Boc;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In a preferred embodiment of the compound according to the invention ofgeneral Formula (I) and in relation to R_(1′) of any of the embodimentsof the present invention,

-   -   the cycloalkyl, aryl or heterocyclyl in R_(1′) if substituted,        is substituted with one or more substituent/s selected from        halogen, —R₁₁, —OR₁₁, —NO₂, —NR₁₁R_(11′″), NR₁₁C(O)R_(11′),        —NR₁₁S(O)₂R_(11′), —S(O)₂NR₁₁R_(11′), —NR₁₁C(O)NR_(11′)R_(11″),        —SR₁₁, —S(O)R₁₁, S(O)₂R₁₁, —CN, haloalkyl, haloalkoxy,        —C(O)OR₁₁, —C(O)NR₁₁R_(11′), —OCH₂CH₂OH,        —NR₁₁S(O)₂NR_(11′)R_(11″) and C(CH₃)₂OR₁₁;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In a preferred embodiment of the compound according to the invention ofgeneral Formula (I) and in relation to R_(1′) of any of the embodimentsof the present invention,

-   -   the cycloalkyl or non-aromatic heterocyclyl in R_(1′), if        substituted, may also be substituted with

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In a preferred embodiment of the compound according to the invention ofgeneral Formula (I) and in relation to R_(1′) of any of the embodimentsof the present invention,

-   -   the alkyl, alkenyl or alkynyl in R_(1′), if substituted, is        substituted with one or more substituent's selected from —OR₁₁,        halogen, —CN, haloalkyl, haloalkoxy and —NR₁₁R_(11′″);

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In a preferred embodiment of the compound according to the invention ofgeneral Formula (I) and in relation to R₂ of any of the embodiments ofthe present invention,

-   -   the cycloalkyl, aryl or heterocyclyl in R₂, if substituted, is        substituted with one or more substituent/s selected from        halogen, —R₁₂, —OR₁₂, —NO₂, —NR₁₂R_(12′″), NR₁₂C(O)R_(12′),        —NR₁₂S(O)₂R_(12′), —S(O)₂NR₁₂R_(12′), —NR₁₂C(O)NR_(12′)R_(12″),        —SR₁₂, —S(O)R₁₂, S(O)₂R₁₂, —CN, haloalkyl, haloalkoxy,        —C(O)OR₁₂, —C(O)NR₁₂R_(12′), —OCH₂CH₂OH,        —NR₁₂S(O)₂NR_(12′)R_(12″) and C(CH₃)₂OR₁₂;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In a preferred embodiment of the compound according to the invention ofgeneral Formula (I) and in relation to R₂ of any of the embodiments ofthe present invention,

-   -   the cycloalkyl or non-aromatic heterocyclyl in R₂, if        substituted, may also be substituted with

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In a preferred embodiment of the compound according to the invention ofgeneral Formula (I) and in relation to R₂ of any of the embodiments ofthe present invention,

-   -   the alkyl, alkenyl or alkynyl in R₂, if substituted, is        substituted with one or more substituent/s selected from —OR₁₂,        halogen, —CN, haloalkyl, haloalkoxy and —NR₁₂R_(12′″);

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In a preferred embodiment of the compound according to the invention ofgeneral Formula (I) and in relation to alkyls other than those definedin R_(1′) or R₂ of any of the embodiments of the present invention,

the alkyl, alkenyl or alkynyl, other than those defined in R_(1′) or R₂,if substituted, is substituted with one or more substituent/s selectedfrom —OR₁₃, halogen, —CN, haloalkyl, haloalkoxy and —NR₁₃R_(13′″);

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In a preferred embodiment of the compound according to the invention ofgeneral Formula (I) and in relation to the cycloalkyl, aryl orheterocyclyl other than those defined in R_(1′) or R₂ of any of theembodiments of the present invention,

the aryl, heterocyclyl or cycloalkyl other than those defined in R_(1′)or R₂, if substituted, is substituted with one or more substituent/sselected from halogen, —R₁₄, —OR₁₄, —NO₂, —NR₁₄R_(14′″),NR₁₄C(O)R_(14′), —NR₁₄S(O)₂R_(14′), —S(O)₂NR₁₄R_(14′),—NR₁₄C(O)NR_(14′)R_(14″), —SR₁₄, —S(O)R₁₄, S(O)₂R₁₄, —CN, haloalkyl,haloalkoxy, —C(O)OR₁₄, —C(O)NR₁₄R_(14′), —OCH₂CH₂OH,—NR₁₄S(O)₂NR_(14′)R_(14″) and C(CH₃)₂OR₁₄;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In a preferred embodiment of the compound according to the invention ofgeneral Formula (I) and in relation to the cycloalkyl, aryl orheterocyclyl other than those defined in R_(1′) or R₂ of any of theembodiments of the present invention,

the cycloalkyl or non-aromatic heterocyclyl, other than those defined inR_(1′) or R₂, if substituted, may also be substituted with

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In an embodiment of the compound according to the invention of generalFormula (I),

the halogen is fluorine, chlorine, iodine or bromine, preferablyfluorine or chlorine;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In an embodiment of the compound according to the invention of generalFormula (I),

the haloalkyl is —CF₃;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

In another embodiment of the compound according to the invention ofgeneral Formula (I),

the haloalkoxy is —OCF₃;

optionally in form of one of the stereoisomers, preferably enantiomersor diastereomers, a racemate or in form of a mixture of at least two ofthe stereoisomers, preferably enantiomers and/or diastereomers, in anymixing ratio, or a corresponding salt thereof, or a correspondingsolvate thereof.

As this invention is aimed at providing a compound or a chemicallyrelated series of compounds which act as ligands of the σ₁ receptor itis a very preferred embodiment in which the compounds are selected whichact as ligands of the σ₁ receptor and especially compounds which have abinding expressed as K_(i) which is preferably <1000 nM, more preferably<500 nM, even more preferably <100 nM.

In the following the phrase “compound of the invention” is used. This isto be understood as any compound according to the invention as describedabove according to general Formula (I), (I′), (I^(a′)), (I^(b′)),(I^(2′)), (I^(3′)) or (I^(4′)).

The compounds of the invention represented by the above describedFormula (I) may include enantiomers depending on the presence of chiralcentres or isomers depending on the presence of multiple bonds (e.g. Z,E). The single isomers, enantiomers or diastereoisomers and mixturesthereof fall within the scope of the present invention.

For the sake of clarity the expression “a compound according to Formula(I), wherein R₁, R₂, R₃, R_(3′), R₅, R_(5′), R₆, R_(6′), R_(n), X, Y, mand n are as defined in the description in the detailed description”would (just like the expression “a compound of Formula (I) as defined inany one of claims 1 to 10” found in the claims) refer to “a compoundaccording to Formula (I)”, wherein the definitions of the respectivesubstituents R₁ etc. (also from the cited claims) are applied. Inaddition, this would also mean, though (especially in regards to theclaims) that also one or more disclaimers defined in the description (orused in any of the cited claims like e.g. claim 1) would be applicableto define the respective compound. Thus, a disclaimer found in e.g.claim 1 would be also used to define the compound “of Formula (I) asdefined in any one of claims 1 to 10”.

In general the processes are described below in the experimental part.The starting materials are commercially available or can be prepared byconventional methods.

A preferred aspect of the invention is also a process for the productionof a compound according to Formula (I).

A preferred aspect of the invention is a process for the production of acompound according to Formula (I),

and wherein R₁, R_(1′), R₂, R₃, R_(3′), R₄, R_(4′), R₅, R_(5′), R₆,R_(6′), m, n, p, X and Y are as defined in the description, followingschemes 1 to 4.

In all processes and uses described underneath, the values of R₁,R_(1′), R₂, R₃, R_(3′), R₄, R_(4′), R₅, R_(5′), R₆, R_(6′), m, n, p, Xand Y are as defined in the description (unless otherwise stated), LGrepresents a leaving group, such as halogen, mesylate, tosylate ortriflate, with the proviso that when Y=CO it can only be chloro orbromo, V represents an aldehyde or another leaving group (such ashalogen, mesylate, tosylate or triflate) and P′ represents a suitableprotecting group (preferably 4-methoxybenzyl or benzyl).

A preferred embodiment of the invention is a process for the productionof a compound according to Formula (I), wherein when R₁ is—(CR₄R₄)_(p)R_(1′), said process comprises:

-   -   a) the intramolecular cyclization of a compound of formula VII

-   -   or    -   b) the reaction of a compound of formula XI

-   -   with a compound of formula XVI

-   -   or    -   c) the incorporation of the group        —N(R_(n))(CR₅R_(5′))_(m)X(CR₆R_(6′))_(n)R₂ by reaction of a        ketone of formula VIIIK

-   -   with an amine of formula XVII

A preferred embodiment of the invention is a process for the productionof a compound according to Formula (I), wherein when R₁ is—(CR₄R_(4′))_(p)R_(1′), said process comprises:

-   -   the intramolecular cyclization of a compound of formula VII

A preferred embodiment of the invention is a process for the productionof a compound according to Formula (I), wherein when R₁ is—(CF₄R_(4′))_(p)R_(1′), said process comprises: the reaction of acompound of formula XI

-   -   with a compound of formula XVI

A preferred embodiment of the invention is a process for the productionof a compound according to Formula (I), wherein when R₁ is—(CR₄R_(4′))_(p)R_(1′), said process comprises: the incorporation of thegroup —N(R_(n))(CR₅R_(5′))_(m)X(CR₆R_(6′))_(n)R₂ by reaction of a ketoneof formula VIIIK

-   -   with an amine of formula XVII

A preferred embodiment of the invention is a process for the productionof a compound according to Formula (I), wherein R₁ is—(CR₄R_(4′))_(p)R_(1′) and wherein Y represents CO and R₃ and R_(3′) aretaken together with the connecting C-atom to form a cycloalkyl (compoundId), said process comprises:

-   -   a) a cyclopropanation reaction of compounds of formula XXII

-   -   or    -   b) the treatment of a compound of formula Ic, wherein r is 1,        and R_(r) and R_(r′) are hydrogen

with a strong base in an aprotic solvent, at a suitable temperature;

or

-   -   c) the reaction of a compound of formula XXVI

-   -   with a compound of formula XVI

A preferred embodiment of the invention is a process for the productionof a compound according to Formula (I), wherein R₁ is—(CR₄R_(4′))_(p)R_(1′), Y represents CO and R₃ and R_(3′) are takentogether with the connecting C-atom to form a cycloalkyl (compound Ib),

said process comprises the treatment of a compound of formula Ic,

with a strong base in an aprotic solvent, at a suitable temperature.

A preferred embodiment of the invention is a process for the productionof a compound according to Formula (I), wherein Y is CH₂ and R₁ is—C(O)—R_(1′) (compound of formula Io), said process comprises:

reacting a compound of formula XXXIV

with an acylating agent of formula XXXVI

In another particular embodiment a compound of Formula II, IIP, III,IMP, XIII, XIIIP, XII, IV, V, VP, VI, XIV, XIVP, X, XP, VII, VHP, XV,XVP, XVK, XI, XIP, XIK, XVI, VIIIP, VIIIK, XVII, Ie, XXIP, XXIK, XXII,XVIIIP, XVIIIK, Ic, XIX, XIXP, XXP, XXK, XXIV, XXIVP, XXIVK, XXVI,XXVIP, XXVIK, XXIIIP, XXIIIK, Ig, XXVP, XXVK, Ih, XXVIIP, XXVI IK,XXVIIIa, XXIXP, XXIXK, XXVIIIb, XXXP, XXXK, XXVI IIe, XVIIIP, XVIIIK,XVII, Im, XXXIIIP, XXXIIIK, In, XXXVP, XXXVK, XXXII, XXXIIP, XXXIIK,XXXIV, XXXIVP, XXXVI, XXXVIIP, XXXVIIK, XXXP, XXXK, XXXIP, XXXIK or XVII

is used for the preparation of a compound of Formula (I).

The obtained reaction products may, if desired, be purified byconventional methods, such as crystallisation and chromatography. Wherethe above described processes for the preparation of compounds of theinvention give rise to mixtures of stereoisomers, these isomers may beseparated by conventional techniques such as preparative chromatography.If there are chiral centers the compounds may be prepared in racemicform, or individual enantiomers may be prepared either byenantiospecific synthesis or by resolution.

One preferred pharmaceutically acceptable form of a compound of theinvention is the crystalline form, including such form in pharmaceuticalcomposition. In the case of salts and also solvates of the compounds ofthe invention the additional ionic and solvent moieties must also benon-toxic. The compounds of the invention may present differentpolymorphic forms, it is intended that the invention encompasses allsuch forms.

Another aspect of the invention refers to a pharmaceutical compositionwhich comprises a compound according to the invention as described aboveaccording to general formula I or a pharmaceutically acceptable salt orsteroisomer thereof, and a pharmaceutically acceptable carrier, adjuvantor vehicle. The present invention thus provides pharmaceuticalcompositions comprising a compound of this invention, or apharmaceutically acceptable salt or stereoisomers thereof together witha pharmaceutically acceptable carrier, adjuvant, or vehicle, foradministration to a patient.

Examples of pharmaceutical compositions include any solid (tablets,pills, capsules, granules etc.) or liquid (solutions, suspensions oremulsions) composition for oral, topical or parenteral administration.

In a preferred embodiment the pharmaceutical compositions are in oralform, either solid or liquid. Suitable dose forms for oraladministration may be tablets, capsules, syrops or solutions and maycontain conventional excipients known in the art such as binding agents,for example syrup, acacia, gelatin, sorbitol, tragacanth, orpolyvinylpyrrolidone; fillers, for example lactose, sugar, maize starch,calcium phosphate, sorbitol or glycine; tabletting lubricants, forexample magnesium stearate; disintegrants, for example starch,polyvinylpyrrolidone, sodium starch glycollate or microcrystallinecellulose; or pharmaceutically acceptable wetting agents such as sodiumlauryl sulfate.

The solid oral compositions may be prepared by conventional methods ofblending, filling or tabletting. Repeated blending operations may beused to distribute the active agent throughout those compositionsemploying large quantities of fillers. Such operations are conventionalin the art. The tablets may for example be prepared by wet or drygranulation and optionally coated according to methods well known innormal pharmaceutical practice, in particular with an enteric coating.

The pharmaceutical compositions may also be adapted for parenteraladministration, such as sterile solutions, suspensions or lyophilizedproducts in the appropriate unit dosage form. Adequate excipients can beused, such as bulking agents, buffering agents or surfactants.

The mentioned formulations will be prepared using standard methods suchas those described or referred to in the Spanish and US Pharmacopoeiasand similar reference texts.

Administration of the compounds or compositions of the present inventionmay be by any suitable method, such as intravenous infusion, oralpreparations, and intraperitoneal and intravenous administration. Oraladministration is preferred because of the convenience for the patientand the chronic character of the diseases to be treated.

Generally an effective administered amount of a compound of theinvention will depend on the relative efficacy of the compound chosen,the severity of the disorder being treated and the weight of thesufferer. However, active compounds will typically be administered onceor more times a day for example 1, 2, 3 or 4 times daily, with typicaltotal daily doses in the range of from 0.1 to 1000 mg/kg/day.

The compounds and compositions of this invention may be used with otherdrugs to provide a combination therapy. The other drugs may form part ofthe same composition, or be provided as a separate composition foradministration at the same time or at different time.

Another aspect of the invention refers to the use of a compound of theinvention or a pharmaceutically acceptable salt or isomer thereof in themanufacture of a medicament.

Another aspect of the invention refers to a compound of the inventionaccording as described above according to general formula I, or apharmaceutically acceptable salt or isomer thereof, for use as amedicament for the treatment of pain. Preferably the pain is medium tosevere pain, visceral pain, chronic pain, cancer pain, migraine,inflammatory pain, acute pain or neuropathic pain, allodynia orhyperalgesia. This may include mechanical allodynia or thermalhyperalgesia.

Another aspect of the invention refers to the use of a compound of theinvention in the manufacture of a medicament for the treatment orprophylaxis of pain.

In a preferred embodiment the pain is selected from medium to severepain, visceral pain, chronic pain, cancer pain, migraine, inflammatorypain, acute pain or neuropathic pain, allodynia or hyperalgesia, alsopreferably including mechanical allodynia or thermal hyperalgesia.

Another aspect of this invention relates to a method of treating orpreventing pain which method comprises administering to a patient inneed of such a treatment a therapeutically effective amount of acompound as above defined or a pharmaceutical composition thereof. Amongthe pain syndromes that can be treated are medium to severe pain,visceral pain, chronic pain, cancer pain, migraine, inflammatory pain,acute pain or neuropathic pain, allodynia or hyperalgesia, whereas thiscould also include mechanical allodynia or thermal hyperalgesia.

The present invention is illustrated below with the aid of examples.These illustrations are given solely by way of example and do not limitthe general spirit of the present invention.

GENERAL EXPERIMENTAL PART (METHODS AND EQUIPMENT OF THE SYNTHESIS ANDANALYSIS

Scheme 1:

A 4-step process is described for the preparation of compounds ofgeneral formula (I) wherein R₁ is —(CR₄R_(4′))_(p)R_(1′) (compounds offormula Ia) starting from a ketone of formula II, as shown in thefollowing scheme:

wherein R_(1′), R₂, R₃, R_(3′), R₄, R_(4′), R₅, R_(5′), R₆, R_(6′),R_(n), X, Y, m, n and p have the meanings as defined above for acompound of formula (I), LG represents a leaving group, such as halogen,mesylate, tosylate or triflate, with the proviso that when Y=CO it canonly be chloro or bromo, V represents an aldehyde or another leavinggroup (such as halogen, mesylate, tosylate or triflate) and P′represents a suitable protecting group (preferably 4-methoxybenzyl orbenzyl).

The 4 step-process is carried out as described below:

Step 1: A compound of formula III is prepared by treating a compound offormula II with a suitable methyl-transfer reagent such astrimethylsulfoxonium iodide or trimethylsulfonium iodide, in a suitableaprotic solvent such as dimethylsulfoxide or 1,2-dimethoxyethane ormixtures, and in the presence of a strong base such as sodium hydride orpotassium tert-butoxide, at a suitable temperature, preferably comprisedbetween 0° C. and 60° C.

Step 2: A compound of formula V is prepared by reacting a compound offormula III with an amine of formula IV, in a suitable solvent such asan alcohol, preferably ethanol-water mixtures, at a suitable temperaturecomprised between room temperature and the reflux temperature.

Step 3: A compound of formula VII is prepared by reacting a compound offormula V with a compound of formula VI. Depending on the meaning of Y,the compound of formula VI can be of different nature and differentreaction conditions will apply:

-   -   a) When Y represents CO, VI is an acylating agent. The acylation        reaction is carried out in a suitable solvent, such as        dichloromethane or ethyl acetate-water mixtures; in the presence        of an organic base such as triethylamine or        diisopropylethylamine or an inorganic base such as K₂CO₃; and at        a suitable temperature, preferably comprised between −78° C. and        room temperature.    -   b) When Y represents CH₂, VI is an alkylating agent. The        alkylation reaction may be carried out in a suitable solvent,        such as acetonitrile, dichloromethane, tetrahydrofuran,        1,4-dioxane or dimethylformamide; in foe presence of an        inorganic base such as K₂CO₃, Cs₂CO₃ or NaH, or an organic base        such as triethylamine or diisopropylethylamine, at a suitable        temperature comprised between room temperature and the reflux        temperature. The OH group present may need protection previous        to the alkylation reaction.

Step 4: The intramolecular cyclization of a compound of formula VIIrenders a compound of formula Ia. The cyclization reaction is carriedout in a suitable solvent, such as tetrahydrofuran; in the presence of astrong base such as potassium tert-butoxide or sodium hydride; and at asuitable temperature, comprised between −78° C. and the refluxtemperature, preferably cooling.

Alternatively, the group —N(R_(n))(CR₅R_(5′))_(m)X(C₆R_(6′))_(n)R₂ canbe incorporated in the last step of the synthesis by reaction of aketone of formula VIIIK with an amine of formula XVII to render acompound of formula Ia, as shown in Scheme 1. A compound of formulaVIIIK is obtained by hydrolysis of a compound of formula VIIIP, whereinA and A′ together with the C atom where they are attached represent asuitable ketal group (cyclic or acyclic). The deprotection can beconducted by adding a solution of an acid such as HCl, in a suitablesolvent such as tetrahydrofuran or water or mixtures, at a suitabletemperature comprised between room temperature and the refluxtemperature, preferably heating. A compound of formula VIIIP is preparedfrom a compound of formula IIP following the same sequence described forthe synthesis of compounds of formula Ia.

The reductive amination reaction between a compound of formula VIIIK anda compound of formula XVII is carried out in the presence of a reductivereagent, preferably sodium triacetoxyborohydride, in an aprotic solvent,preferably tetrahydrofuran, dichloromethane or dichloroethane,optionally in the presence of an acid, preferably acetic acid.

In another alternative approach, the —(CR₄R_(4′))_(p)R_(1′) substituentcan be incorporated later in the sequence by the reaction of a compoundof formula XI with a compound of formula XVI. Depending on the meaningof Y, V can be of different nature and different reaction conditionswill apply:

-   -   a) When Y is CH₂, compound XVI is an alkylating agent and V        represents a leaving group such as halogen, mesylate, tosylate        or triflate. The alkylation reaction is carried out in a        suitable solvent, such as acetonitrile, dichloromethane,        1,4-dioxane or dimethylformamide; in the presence of an        inorganic base such as K₂CO₃, Cs₂CO₃ or sodium hydride, or an        organic base such as triethylamine or diisopropylethylamine, at        a suitable temperature comprised between room temperature and        the reflux temperature. Additionally, an activating agent such        as NaI can be used.        -   Alternatively, compound XVI can be an aldehyde wherein V            represents a C(O)—H group. The reductive amination reaction            between a compound of formula XVI and a compound of formula            XI is carried out under the same reaction conditions            described above for the reaction of a compound of formula            VIIIK and a compound of formula XVII.    -   b) When Y is —C(O), compound XVI is an alkylating agent and V        represents a leaving group such as halogen, mesylate, tosylate        or triflate. This alkylation reaction is carried out in an        aprotic solvent, preferably dimethylformamide or        tetrahydrofuran, in the presence of an inorganic base such as        NaH, at a suitable temperature, preferably between room        temperature and 60° C.

A compound of formula XI is synthesized following an analogous sequenceas described for the synthesis of compounds of formula Ia, but effectingstep 2 using ammonia instead of an amine IV. Alternatively, when Y isC(O), a compound of formula XI can be prepared by reaction of a compoundof formula XIK (prepared from a compound of formula XIP, wherein A andA′ together with the C atom where they are attached represent a suitableketal group) with a compound of formula XVII, as described above.

Additionally, a compound of formula XI can be prepared from a compoundof formula XV, wherein P′ represents a suitable protecting group. When Yis C(O), P′ is preferably a 4-methoxybenzyl group and the deprotectionreaction is carried out with cerium ammonium nitrate in a suitablesolvent such as mixtures of acetonitrile-water or by heating intrifluoroacetic add or hydrochloric add. When Y is —CH₂—, P′ ispreferably a 4-methoxybenzyl or a benzyl group, and the deprotectionreaction is preferably carried out by hydrogenation under hydrogenatmosphere and metal catalysis, preferably by the use of palladium overcharcoal as catalyst in a suitable solvent such as methanol or ethanol,optionally in the presence of an add such as acetic acid or hydrochloricadd.

A compound of formula XV is synthesized from a compound of formula IIIand an amine of formula XII following an analogous sequence as describedfor the synthesis of compounds of formula Ia. Alternatively, a compoundof formula XV can be prepared by reaction of a compound of formula XVK(prepared from a compound of formula XVP, wherein A and A′ together withthe C atom where they are attached represent a suitable ketal group)with a compound of formula XVII, as described above.

The compounds of general formula II, IIP, IV, VI, XII, XVI and XVII arecommercially available or can be prepared by conventional methodsdescribed in the bibliography.

Scheme 2

The preparation of compounds of general formula (I) wherein Y representsCO and R₃ and R_(3′) are taken together with the connecting C-atom toform a cycloalkyl (compounds of formula Ib) is described in thefollowing scheme:

Wherein R_(1′), R₂, R₄, R_(4′), R₅, R_(5′), R₆, R_(6′), R_(n), X, m, nand p have the meanings as defined above for a compound of formula (I),r represents 1, 2, 3 or 4, R_(r) and R_(r′) represent hydrogen or anysubstitution according to the present invention, LG represents a leavinggroup such as halogen, mesylate, tosylate or triflate, V representsanother leaving group (such as halogen, mesylate, tosylate or triflate),P′ represents a suitable protecting group (preferably 4-methoxybenzyl)and Q represents methyl or benzyl.

A compound of formula Ib can be prepared from a compound of formula Icby treatment with a strong base such as lithium diisopropylamide orpotassium tert-butoxide, in an aprotic solvent such as tetrahydrofuran,at a suitable temperature, preferably cooling. And analogously, acompound of formula Id (wherein R_(r)=R_(r′)=H and r=1) can be preparedfrom a compound of formula Ic under the same reaction conditions.

Alternatively, compounds of formula Id can be prepared from compounds offormula XXII. The cyclopropanation reaction is carried out using asuitable methyl-transfer reagent such as trimethylsulfoxonium iodide ortrimethylsulfonium iodide, in a suitable aprotic solvent such asdimethylsulfoxide, and in the presence of a strong base such as sodiumhydride or potassium tertbutoxide, at a suitable temperature, preferablycomprised between room temperature and 60° C. Alternatively, typicalSimmons-Smith reaction conditions could be used, comprising thetreatment of a compound of formula XXII with diiodomethane, a zincsource such as zinc-copper, zinc iodide or diethylzinc, in a suitableaprotic solvent, such as diethyl ether.

Compounds of formula XXII can be prepared from a compound of formula Iewherein Q represents methyl or benzyl. The elimination reaction iscarried out in the presence of a base, such as potassium tertbutoxide,in a suitable solvent, such as tetrahydrofuran.

In another alternative approach, the —(CR₄R_(4′))_(p)R_(1′) substituentcan be incorporated later in the synthesis. Thus, compounds of formulaIb and Id can be prepared from compounds of formula XXIV and XXVI,respectively, following the reaction conditions described in Scheme 1for the preparation of compounds of formula Ia from compounds of formulaXI. The compounds of formula XXIV and XXVI can be prepared from suitableprotected precursors If and Ig, respectively, following the conditionsdescribed in Scheme 1.

The protected compounds of general formula If and Ig can be preparedfollowing an analogous procedure to the one described in Scheme 2 forthe preparation of compounds Ib and Id from compounds of formula Ic,using suitable precursors.

In addition, the group —N(R_(n))(CR₅R_(5′))_(m)X(CR₆R_(6′))_(n)R₂ can beincorporated in the last step of the synthesis to prepare compounds offormula Ib, Id, Ie, If, Ig, XXIV and XXVI from suitable protectedprecursors, by deprotection followed by reaction with a compound offormula XVII, as described in Scheme 1 for the preparation of compoundsof formula Ia.

The compounds of general formula Ic and Ie can be prepared by theprocedures described in Scheme 1 from a compound of formula V usingsuitable starting materials.

Scheme 3 and Scheme 4

Compounds of formula (I) can also be prepared starting from othercompounds of formula (I), as described in Schemes 3 and 4 below.

Compounds of formula Ib, Ii and Ij can be prepared from a compound offormula Ih as shown in Scheme 3:

wherein R_(1′), R₂, R₃, R_(3′), R₄, R_(4′), R₅, R_(5′), R₆, R_(6′),R_(n), X, m, n and p have the meanings as defined above for a compoundof formula (I), r represents 1, 2, 3 or 4, R_(r) and R_(r′) representhydrogen or any substitution according to the present invention, and X′and X″ independently represent a leaving group such as halogen,mesylate, tosylate or triflate.

A compound of formula Ii can be prepared by treating a compound offormula Ih with an alkylating agent of formula XXVIIIa in the presenceof a strong base such as lithium diisopropylamide or potassiumtert-butoxide, in an aprotic solvent such as tetrahydrofuran, at asuitable temperature, preferably comprised between −78° C. and roomtemperature. A second alkylation can be performed under the samereaction conditions to prepare a compound of formula Ij. An analogousdouble-alkylation process can be used for the preparation of compoundsof formula Ib, by reacting a compound of formula Ih with an alkylatingagent of formula XXVIIIc, as an alternative to the procedure describedin Scheme 2 for the preparation of compounds of formula Ib.

In addition, the group —N(R_(n))(CR₅R_(5′))_(m)X(CR₆R_(6′))_(n)R₂ can beincorporated in the last step of the synthesis to prepare compounds offormula Ib, Ih, Ii and Ij from suitable protected precursors, bydeprotection followed by reaction with a compound of formula XVII, underthe reaction conditions described in Scheme 1 for the preparation ofcompounds of formula Ia.

The compounds of general formula Ih and Ii can be prepared by theprocedures described in Scheme 1 using suitable starting materials.

Scheme 4 shows the preparation of compounds of formula (I) wherein Y isCH₂ from compounds of formula (I) wherein Y is C(O):

wherein R_(1′), R₂, R₃, R_(3′), R₄, R_(4′), R₅, R_(5′), R₆, R_(6′),R_(n), X, m, n and p have the meanings as defined above for a compoundof formula (I), V represents an aldehyde or a leaving group (such ashalogen, mesylate, tosylate or triflate), P′ represents a suitableprotecting group (preferably 4-methoxybenzyl or benzyl) and Z representsOH or halogen (preferably bromo or chloro).

The reduction reaction of a compound of formula Ij or Io to yield acompound of formula Ik can be performed using a suitable reducing agentsuch as lithium aluminium hydride, borane-tetrahydrofuran complex orborane-dimethyl sulphide complex, in a suitable solvent such astetrahydrofuran or diethyl ether, at a suitable temperature comprisedbetween room temperature and the reflux temperature, preferably heating.

The reduction reaction can also be performed on a suitable precursor(compounds of formula Im or XXXII) or a protected derivative (compoundsof formula XXXIIIP, XXXIIP or XXXVIF).

The compounds of general formula Ij can be prepared by the proceduresdescribed in Schemes 1 to 3 using suitable starting materials, or theycan be prepared from a compound of formula Im or XXXII. The deprotectionof a compound of formula Im to give a compound of formula XXXII and thesubsequent reaction with a compound of formula XVI to yield a compoundof formula Ij are performed following the procedures described in Scheme1.

The compounds of general formula Im and XXXII can be prepared accordingto the procedures described in Scheme 1 using suitable startingmaterials.

Accordingly, the compounds of general formula Ik may be prepared from acompound of formula In or XXXIV following an analogous procedure.

A compound of formula Io is prepared by reading a compound of formulaXXXIV with an acylating agent of formula XXXVI. When Z is halogen, thereaction is carried out in a suitable solvent, such as dichloromethane,tetrahydrofuran, ethyl acetate or ethyl acetate-water mixtures; in thepresence of an organic base such as triethylamine ordiisopropylethylamine or an inorganic base such as K₂CO₃; and at asuitable temperature, preferably comprised between 0° C. and roomtemperature. Additionally, an activating agent such as4-dimethylaminopyridine can be used.

When Z is OH, the acylation reaction is carried out using a suitablecoupling reagent such as N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide(EDC), dicyclohexylcarbodiimide (DCC),N-[(dimethylamino)-1H-1,2,3-triazolo-[4,5b]pyridin-1-ylmethylene]-N-methylmethanaminium hexafluorophosphate N-oxide (HATU) orN,N,N′,N′-tetramethyl-O-(1H-benzotriazol-1-yl)uroniumhexafluorophosphate (HBTU), optionally in the presence of1-hydroxybenzotriazole, optionally in the presence of an organic basesuch as N-methylmorpholine or diisopropylethylamine, in a suitablesolvent such as dichloromethane or dimethylformamide, and at a suitabletemperature, preferably at room temperature.

In addition, the group —N(R_(n))(CR₅R_(5′))_(m)X(CR₆R_(6′))_(n)R₂ may beincorporated at different stages of the synthesis to prepare compoundsof formula Ik and Io from suitable precursors and a compound of formulaXVII, following similar reaction conditions as described in Scheme 1 forthe preparation of compounds of formula Ia.

Moreover, certain compounds of the present invention can also beobtained starting from other compounds of formula (I) by appropriateconversion reactions of functional groups, in one or several steps,using well-known reactions in organic chemistry under standardexperimental conditions. As a way of example, some of these conversionsinclude the N-debenzylation of an amine to yield a NH group, and thealkylation or reductive amination of a secondary amine to yield atertiary amine.

In addition, a compound of formula I that shows chirality can also beobtained by resolution of a racemic compound of formula I either bychiral preparative HPLC or by crystallization of a diastereomeric saltor co-crystal. Alternatively, the resolution step can be carried out ata previous stage, using any suitable intermediate.

EXAMPLES Intermediates and Examples

The following abbreviations are used in the examples:

ACN: acetonitrile

AcOH: acetic acid

DCM: dichloromethane

DME: 1,2-dimethoxyetane

DMSO: dimethyl sulfoxide

EtOH: Ethanol

EX: example

h: hour/s

HPLC: high performance liquid chromatography

INT: intermediate

LDA: lithium diisopropylamide

MeOH: methanol

MS: mass spectrometry

Min.: minutes

Quant: quantitative

Ret.: retention

r.t.: room temperature

Sat: saturated

s.m.: starting material

TFA: trifluoroacetic add

THF: tetrahydrofuran

Wt: weight

The following method was used to determine the HPLC-MS spectra:

Column: Gemini-NX 30×4.6 mm, 3 um

Temperature: 40° C.

Flow: 2.0 mL/min

Gradient: NH₄HCO₃ pH 8: ACN (95:5)—0.5 min—(95:5)—6.5 min—(0:100)—1min—(0:100)

Sample dissolved aprox. 1 mg/mL in NH₄HCO₃ pH 8/ACN

Alternatively, method B was used in some cases and is indicated inexamples and tables as (B):

Method B

Column: Kinetex EVO 50×4.6 mm 2.6 um

Temperature: 40° C.

Flow: 2.0 mL/min

Gradient: NH₄HCO₃ pH 8: ACN (95:5)—0.5 min—(95:5)—6.5 min—(0:100)—1min—(0:100)

Sample dissolved aprox. 1 mg/mL in NH₄HCO₃ pH 8/ACN

Synthesis of Intermediates Intermediate 1:1,7,10-Trioxadispiro[2.2.4.2]dodecane

To a solution of potassium tert-butoxide (14.5 g, 130 mmol) in DMSO (83mL), trimethylsulfoxonium iodide (31.8 g, 144 mmol) was added inportions. The mixture was stirred at r.t. for 1.5 h. DME (23 mL) wasadded and it was cooled to 0-5° C. A solution of1,4-dioxaspiro[4.5]decan-8-one (15.56 g, 99.6 mmol) in a mixture of DME(23 mL) and DMSO (7.5 mL) was added dropwise. The reaction mixture wasstirred at 0-5° C. for 1 h. It was diluted with water and ethyl acetate.The phases were separated and the aqueous phase was back extracted withadditional ethyl acetate. The organic phases were combined, washed withwater, dried over MgSO₄ and concentrated under vacuum to give the titlecompound (12.3 g, 72% yield).

Intermediate 2A: 8-((Ethylamino)methyl)-1,4-dioxaspiro[4.5]decan-8-ol

To a solution of intermediate 1 (5.0 g, 29.4 mmol) in a mixture ofethanol-water 9:1 (50 mL), ethylamine (46.7 mL, 70% solution in water,587 mmol) was added. The reaction mixture was stirred at r.t. overnight.The solvent was removed under vacuum to give the tide compound (6.3 g,quant, yield).

Intermediate 2B: 8-((Phenylamino)methyl)-1,4-dioxaspiro[4.5]decan-8-ol

To a solution of intermediate 1 (7.09 g, 41.7 mmol) in a mixture ofethanol-water 9:1 (140 mL), aniline (3.8 mL, 41.7 mmol) was added. Thereaction mixture was heated to 100° C. overnight in an autoclavereactor. The solvent was removed under vacuum and the residue waspurified by flash chromatography, silica gel, gradient dichloromethaneto methanol:dichloromethane (1:4) to give the title compound (6.37 g,58% yield).

Intermediate 2C:8-(((4-Methoxybenzyl)amino)methyl)-1,4-dioxaspiro[4.5]decan-8-ol

To a solution of intermediate 1 (14.9 g, 87.5 mmol) in a mixture ofEtOH—H₂O 9:1 (75 mL), 4-methoxybenzylamine (11.4 mL, 87.5 mmol) wasadded. The reaction mixture was stirred at r.t. overnight. The solventwas removed under vacuum to give the title compound (29.3 g, overweight,quant, yield assumed).

Intermediate 3A:16-Ethyl-4,9,12-trioxa-16-azatrispiro[2.1.2.4.2.3]heptadecan-17-one

Step 1.2-Bromo-4-chloro-N-ethyl-N-((8-hydroxy-1,4-dioxaspiro[4.5]decan-8-yl)methyl)butanamide:To a solution of intermediate 2A (6.32 g, 29.4 mmol) in ethyl acetate(63 mL), a solution of K₂CO₃ (11.4 g, 82.2 mmol) in water (43 mL) wasadded. After cooling to 0-5° C., a solution of 2-bromo-4-chlorobutanoylchloride (prepared as described in U.S. Pat. No. 6,114,641A1 (2000) Ex1)(8.78 g, 39.9 mmol) in ethyl acetate (15 mL) was added dropwise. Thereaction mixture was stirred at 0-5° C. for 1 h and then it was dilutedwith water. The layers were separated and the aqueous phase wasextracted with ethyl acetate. The organic phases were combined, washedwith 0.5 M HCl aqueous solution and then NaHCO₃ sat solution, dried overMgSO₄, filtered and concentrated to dryness to give the title compound(9.86 g, crude product, 84% yield).

Step 2. Title compound: A solution of the crude product obtained in step1 (8.86 g, 22.2 mmol) in THF (89 mL) was cooled under nitrogen to −78°C. After addition of potassium tert-butoxide solution (44.5 mL, 1M inTHF, 44.5 mmol), the reaction mixture was stirred at −30° C. for 2 h. Itwas then warmed-up to 0−5° C. and additional potassium tert-butoxidesolution (44.5 mL, 1M in THF, 44.5 mmol) was added. The mixture wasstirred at 0-5° C. for 2 h. NH₄Cl sat solution was then added, it wasfurther diluted with water and the aqueous phase was extracted 3 timeswith ethyl acetate. The organic phases were combined, dried over MgSO₄,filtered and concentrated under vacuum to give the title compound (5.49g, 88% yield).

This method was used for the preparation of intermediates 3B-3C usingsuitable starting materials:

INT Structure Chemical name s.m. 3B

16-phenyl-4,9,12-trioxa-16- azatrispiro[2.1.2.4.2.3]heptedecan- 17-one2B 3C

16-(4-methoxybenzyl)- 4,9,12-trioxa-16-azatrispiro[2.1.2.4.2.3]heptadecan- 17-one 2C

Intermediate 3D:12-Ethyl-1,4,9-trioxa-12-azadispiro[4.2.5.2]pentadecan-11-one

Step 1.2-Chloro-N-ethyl-N-((8-hydroxy-1,4-dioxaspiro[4.5]decan-8-yl)methyl)acetamide:To a solution of intermediate 2A (6 g, 27.9 mmol) in ethyl acetate (60mL), a solution of K₂CO₃ (10.8 g, 78.0 mmol) in water (42 mL) was added.After cooling to 0° C., a solution 2-chloroacetyl chloride (4.28 g, 37.9mmol) in ethyl acetate (15 mL) was added dropwise. The reaction mixturewas stirred at 0-5° C. for 1 h and then it was diluted with water. Thelayers were separated and the aqueous phase was extracted with ethylacetate. The organic phases were combined, washed with 0.5 M HCl aqueoussolution and then NaHCO₃ sat solution, dried over MgSO₄, filtered andconcentrated to dryness to give the title compound (4.94 g, 61% yield).

Step 2. Title compound: A solution of the crude product obtained in Step1 (4.93 g, 16.9 mmol) in THF (50 mL) was cooled to −78° C. using a dryice/acetone bath. After addition of potassium tert-butoxide solution(25.4 mL, 1M in THF, 25.4 mmol), the reaction mixture was stirred at−78° C. for 1 h. NH₄Cl sat solution was then added, and the aqueousphase was extracted with ethyl acetate (×3). The organic phases werecombined, dried over MgSO₄, filtered and concentrated under vacuum togive the tide compound (3.77 g, 87% yield).

Intermediate 3E:12-Ethyl-10,10-dimethyl-1,4,9-trioxa-12-azadispiro[4.2.5.2]pentadecan-11-one

Step 1.12-Ethyl-10-methyl-1,4,9-trioxa-12-azadispiro[4.2.5.2]pentadecan-11-one.The product was prepared following the procedure described for thepreparation of Intermediate 3D, starting from intermediate 2A and2-chloropropanoyl chloride.

Step 2. Title compound: A solution of the product obtained in Step 1(7.5 g, 27.8 mmol) in dry THF (39 mL) was cooled to 0-5° C. under anitrogen atmosphere. After slow addition of LDA solution (37.2 mL, 1.5 Min THF/n-heptane/ethylbenzene, 55.8 mmol), the reaction mixture wasstirred at 0-5° C. for 30 min. Iodomethane (5.2 mL, 83.5 mmol) was thenadded and the reaction mixture was stirred at 0-5° C. for further 60min. A second round of LDA solution and iodomethane were added to getthe reaction to completion. NH₄Cl sat solution was then added, and theaqueous phase was extracted three times with ethyl acetate. The combinedorganic phases were dried over Na₂SO₄, filtered and concentrated undervacuum. The residue was purified by flash chromatography, silica gel,gradient dichloromethane to methanol:dichloromethane (1:8) to give thetitle compound (5.02 g, 62% yield).

Intermediate 4A: 12-Ethyl-4-oxa-12-azadispiro[2.1.5.3]tridecane-8,13-dione

To a solution of intermediate 3A (6.1 g, 21.7 mmol) in THF (116 mL), 6 MHCl aqueous solution (36 mL, 217 mmol) was added. The reaction mixturewas heated to 50° C. for 2 days in a sealed vessel. The volatiles wereremoved under vacuum and pH was adjusted to 7 with addition of NaHCO₃sat solution. The aqueous phase was extracted 3 times with ethylacetate. The organic phases were combined, washed with brine, dried overMgSO₄, filtered and concentrated under vacuum to give the title compound(5.15 g, crude product, quant, yield).

This method was used for the preparation of intermediate 4B usingsuitable starting materials:

INT Structure Chemical name s.m. 4B

12-phenyl-4-oxa-12- azadispiro[2.1.5.3]- tridecane-8,13-dione 3B

Intermediate 4C: 4-Ethyl-1-oxa-4-azaspiro[5.5]undecane-3,9-dione

A solution of intermediate 3D (1.11 g, 4.35 mmol) in TFA (16.8 mL) washeated to 80° C. for 2 days in a sealed vessel. The volatiles wereremoved under vacuum to give the title compound as a crude product (1.81g, overweight, quant, yield assumed).

This method was used for the preparation of intermediates 4D-E usingsuitable starting materials:

INT Structure Chemical name s.m. 4D

4-ethyl-2,2- dimethyl-1-oxa-4- azaspiro[5.5]- undecane-3,9-dione 3E 4E

4-oxa-12- azadispiro[2.1.5.3]- tridecane-8,13- dione 3C

Intermediates 5A and 5B:(5s,8s)-8-(Benzylamino)-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one and(5r,8r)-8-(benzylamino)-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one

To a solution of intermediate 4E (2.8 g, 13.4 mmol) in dry THF (138 mL),benzylamine (1.46 mL, 13.4 mmol) and sodium triacetoxyborohydride (3.77g, 17.8 mmol) were added. The resulting mixture was stirred at r.t.overnight. 1N NaOH was added and it was extracted with DCM. The organicphases were combined, dried over Na₂SO₄, filtered and concentrated todryness. The residue was purified by flash chromatography, C₁₈, gradientaqueous NH₄HCO₃ pH 8 to acetonitrile, to give intermediates 5A (856 mg,21% yield) and 5B (209 mg, 5% yield).

Synthesis of Examples Examples 1 and 2:(5s,8s)-8-(Benzylamino)-12-ethyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-oneand(5r,8r)-8-(benzylamino)-12-ethyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one

To a solution of intermediate 4A (90 mg, 0.38 mmol) in dry THF (3.8 mL),benzylamine (0.041 mL, 0.38 mmol), acetic acid (0.022 mL, 0.38 mmol) andsodium triacetoxyborohydride (107 mg, 0.50 mmol) were sequentiallyadded. The resulting mixture was stirred at r.t. for 4 h. 1N NaOH wasadded and it was extracted with DCM. The organic phases were combined,dried over Na₂SO₄, filtered and concentrated to dryness. The residue waspurified by flash chromatography, C₁₈, gradient aqueous NH₄HCO₃ pH 8 toacetonitrile, obtaining examples 1 (25 mg, 20% yield) and 2 (27 mg, 22%yield)

HPLC retention time (Ex 1): 3.08 min; MS: 329.2 (M+H).

HPLC retention time (Ex 2): 3.36 min; MS: 329.2 (M+H).

This method was used for the preparation of examples 3-13 using suitablestarting materials:

Ret time MS EX Structure Chemical name (min) (M + H) 3

(5s,8s)-12-ethyl-8- [methyl(2- phenylethyl)amino]-4- oxa-12-azadispiro[2.1.5.3]- tridecan-13-one 3.61 357.2 4

(5r,8r)-12-ethyl-8- [methyl(2- phenylethyl]amino]-4- oxa-12-azadispiro[2.1.5.3]- tridecan-13-one 3.90 357.2 5

(5s,8s)-8- [benzyl(methyl)amino]- 12-ethyl-4-oxa-12-azadispiro[2.1.5.3]- tridecan-13-one 3.82 343.2 6

(5s,8s)-12-ethyl-8-[(2- phenylethyl)amino]-4- oxa-12-azadispiro[2.1.5.3]- tridecan-13-one 3.16 343.2 7

(5r,8r)-12-ethyl-8-[(2- phenylethyl)amino]-4- oxa-12-azadispiro[2.1.5.3]- tridecan-13-one 3.39 343.2 8

(5s,8s)-8- [benzyl(methyl)amino]- 12-phenyl-4-oxa-12-azadispiro[2.1.5.3]- tridecan-13-one 4.59 391.2 9

(5s,8s)-8-[methyl(2- phenylethyl)amino]- 12-phenyl-4-oxa-12-azadispiro[2.1.5.3]- tridecan-13-one 4.40 405.2 10 

(5s,8s)-8- (benzylamino)-12- phenyl-4-oxa-12- azadispiro[2.1.5.3]-tridecan-13-one 3.87 377.2 11 

(5s,8s)-12-phenyl-8-[(2- phenylethyl)amino]-4- oxa-12-azadispiro[2.1.5.3]- tridecan-13-one 3.90 391.2 12 

(5r,8r)-8- (benzylamino)-12- phenyl-4-oxa-12- azadispiro[2.1.5.3]-tridecan-13-one 4.08 377.2 13 

(5r,8r)-12-phenyl-8-[(2- phenylethyl)amino]-4- oxa-12-azadispiro[2.1.5.3]- tridecan-13-one 4.05 391.2

Example 14:(5r,8r)-8-[Benzyl(methyl)amino]-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one

To a solution of example 12 (37 mg, 0.098 mmol) in MeOH (0.4 mL),aqueous formaldehyde (0.13 mL, 37% Wt, 1.77 mmol) was added. Thereaction mixture was stirred at r.t. for 30 min. and then sodiumtriacetoxyborohydride (62 mg, 0.295 mmol) was added in portions. Theresulting mixture was stirred at r.t. for 5 h. NaHCO₃ sat solution wasadded and it was extracted with DCM. The organic phases were combined,dried over Na₂SO₄, filtered and concentrated to dryness. The residue waspurified by flash chromatography, Cis, gradient aqueous NH₄HCO₃ pH 8 toacetonitrile, to give the title compound (15 mg, 39% yield).

HPLC retention time: 4.76 min; MS: 391.2 (M+H).

This method was used for the preparation of examples 15-16 usingsuitable starting materials:

Ret Chemical time MS EX Structure name (min) (M + H) 15

(5r,8r)-8- [methyl(2- phenylethyl)- amino]- 12-phenyl- 4-oxa-12-azadispiro- [2.1.5.3]- tridecan- 13-one 4.59 405.2 16

(5r,8r)-8- [benzyl- (methyl)- amino]- 12-ethyl-4- oxa-12- azadispiro-[2.1.5.3]- tridecan- 13-one 4.30 (B) 343.2

Example 17:(5s,8s)-N-Benzyl-12-ethyl-N-methyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-8-amine

To a solution of example 5 (0.105 g, 0.30 mmol) in THF (0.2 mL), cooledat 0° C., LiAlH₄ solution (0.41 mL, 1M in THF, 0.41 mmol) was addeddropwise. The reaction mixture was stirred at r.t. for 2 h. Then, NaHCO₃sat solution was added and it was extracted with ethyl acetate. Theorganic phases were combined, washed with water, dried over Na₂SO₄,filtered and concentrated to dryness. The residue was purified byeluting through an acidic ion exchange resin cartridge (SCX), to givethe title compound (73 mg, 73% yield).

HPLC retention time: 4.28 min; MS: 329.2 (M+H).

This method was used for the preparation of examples 18-20 usingsuitable starting materials:

Ret MS Chemical time (M + EX Structure name (min) H) 18

(5r,8r)- N- benzyl- 12- ethyl-N- methyl- 4-oxa- 12-aza- dispiro-[2.1.5.3]- tridecan- 8-amine 4.50 329.2 19

(5s,8s)- N- benzyl- N- methyl- 12- phenyl- 4- oxa-12- aza- dispiro-[2.1.5.3]- tridecan- 8-amine 5.66 377.2 20

(5r,8r)- N- benzyl- N- methyl- 12- phenyl- 4- oxa-12- aza- dispiro-[2.1.5.3]- tridecan- 8-amine 5.78 377.2

Example 21:(5r,8r)-8-<Methylamino)>12-ethyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-oneacetate

A mixture of example 16 (0.279 g, 0.81 mmol), AcOH (0.047 mL, 0.81 mmol)and palladium (30 mg, 10% wt on carbon) in MeOH (3 mL) was stirred under3 bars of H₂ at 50° C. for 1 day. The catalyst was filtered off and thesolvent was removed under vacuum to give the title compound (253 mg, 99%yield).

HPLC retention time: 1.64 min; MS: 253.2 (M+H).

This method was used for the preparation of examples 22-26 usingsuitable starting materials:

Ret time MS EX Structure Chemical name (min) (M + H) 22

(5s,8s)-12-ethyl-8- (methylamino)-4- oxa-12- azadispiro[2.1.5.3]-tridecan-13-one acetate 1.39 253.2 23

(5s,8s)-8- (methylamino)-12- phenyl-4-oxa-12- azadispiro[2.1.5.3]-tridecan-13-one acetate 2.40 301.1 24

(5r,8r)-8- (methylamino)-12- phenyl-4-oxa-12- azadispiro[2.1.5.3]-tridecan-13-one acetate 2.34 301.1 25

(5s,8s)-N-methyl- 12-phenyl-4-oxa-12- azadispiro[2.1.5.3]-tridecan-8-amine acetate 3.04 287.2 26

(5r,8r)-N-methyl-12- phenyl-4-oxa-12- azadispiro[2.1.5.3]-tridecan-8-amine acetate 3.10 287.2

Example 27:(5r,8r)-12-Ethyl-8-[methyl(3-methylbutyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one

A mixture of example 21 (0.253 g, 0.81 mmol), 1-bromo-3-methylbutane(0.15 mL, 0.13 mmol) and K₂CO₃ (0.56 g, 4.06 mmol) in acetonitrile (2.5mL) was heated at 80° C. in a sealed tube overnight. 1M NaOH aqueous solwas added and it was extracted with ethyl acetate. The organic phaseswere combined, dried over MgSO₄, filtered and concentrated to dryness.The residue was purified by flash chromatography, C₁₈, gradient aqueousNH₄HCO₃ pH 8 to acetonitrile, to give the title compound (103 mg, 39%yield).

HPLC retention time: 3.39 min; MS: 323.2 (M+H).

This method was used for the preparation of examples 28-34 usingsuitable starting materials:

Ret time MS EX Structure Chemical name (min) (M + H) 28

(5s,8s)-12-ethyl-8- [methyl(3-methyl- butyl)amino]- 4-oxa-12-azadispiro[2.1.5.3]- tridecan-13-one 3.13 (B) 323.2 29

(5s,8s)-8-[methyl(3- methylbutyl)amino]- 12-phenyl-4-oxa-12-azadispiro-[2.1.5.3]- tridecan-13-one 3.79 371.2 30

(5r,8r)-8- [methyl(3- methylbutyl)amino]- 12-phenyl-4-oxa-12-azadispiro-[2.1.5.3]- tridecan-13-one 4.01 371.2 31

(5s,8s)-N-methyl- N-(3-methylbutyl)- 12-phenyl-4-oxa-12-azadispiro-[2.1.5.3]- tridecan-8-amine 4.85 357.3 32

(5r,8r)-N-methyl-N- (3-methylbutyl)-12- phenyl-4-oxa-12-azadispiro-[2.1.5.3]- tridecan-8-amine 4.96 357.3 33

(5s,8s)-12-ethyl-8- [methyl(2- methylpropyl)amino]- 4-oxa-12-azadispiro-[2.1.5.3]tridecan- 13-one 3.00 (B) 309.2 34

(5r,8r)-N-methyl-12- phenyl-N-(2- phenylethyl)-4-oxa-12-azadispiro-[2.1.5.3]- tridecan-8-amine 5.68 (B) 391.2

Example 35:(5r,8r)-12-Ethyl-N-methyl-N-(3-methylbutyl)-4-oxa-12-azadispiro[2.1.5.3]tridecan-8-amine

To a solution of example 27 (64 mg, 0.19 mmol) in THF (0.4 mL),borane-tetrahydrofuran complex solution (0.6 mL, 1M in THF, 0.6 mmol)was added dropwise at r.t. The reaction mixture was stirred at 65° C.for 2 h, then it was cooled to r.t. Additional borane-tetrahydrofurancomplex solution (0.5 mL, 1M in THF, 0.5 mmol) was added and it wasstirred at 65° C. for 5 h. 1M NaOH aqueous sol (0.12 mL) was carefullyadded, cooling the mixture with an ice-water bath, and then it washeated to 70° C. for 6 h. After cooling to r.t., THF was evaporated andit was diluted with ethyl acetate. The phases were separated and theaqueous phase was back extracted with ethyl acetate. The organic phaseswere combined, dried over MgSO₄, filtered and concentrated to dryness.The residue was purified by flash chromatography, silica gel, gradientDCM to MeOH:DCM (1:4) to give the title compound (20 mg, 33% yield).

HPLC retention time: 3.68 min; MS: 309.2 (M+H).

Examples 36 to 40 were prepared according to the procedure described inExample 1, using suitable starting materials:

Ret MS Chemical time (M + EX Structure name (min) H) 36

(6s,9s)-9- (benzylamino)- 4-ethyl-1-oxa- 4-azaspiro[5.5]- undecan-3-one2.98 (B) 303.2 37

(6r,9r)-9- (benzylamino)- 4-ethyl-1-oxa- 4-azaspiro[5.5]- undecan-3-one3.11 (B) 303.2 38

(6s,9s)-4-ethyl- 9-(isobutyl- (methyl)- amino)-1-oxa- 4-azaspiro[5.5]-undecan-3-one 2.46 283.2 39

(6s,9s)-9- (benzyl- amino)-4- ethyl-2,2- dimethyl-1- oxa-4-azaspiro[5.5]- undecan-3-one 3.26 331.2 40

(6r,9r)-9- (benzyl- amino)-4- ethyl-2,2- dimethyl-1- oxa-4-azaspiro[5.5]- undecan-3-one 3.48 331.2

Examples 41 to 44 were prepared according to the procedure described inExample 14, using suitable starting materials:

Ret MS time (M + EX Structure Chemical name (min) H) 41

(6s,9s)-9- (benzyl(methyl)- amino)-4- ethyl-1- oxa-4- azaspiro[5.5]-undecan-3-one 3.34 317.2 42

(6r,9r)-9- (benzyl(methyl)- amino)-4- ethyl-1- oxa-4- azaspiro[5.5]-undecan-3-one 3.55 317.2 43

(6s,9s)-9- (benzyl(methyl)- amino)-4- ethyl-2,2- dimethyl- 1-oxa-4-azaspiro[5.5]- undecan-3-one 4.19 (B) 345.2 44

(6r,9r)-9- (benzyl(methyl)- amino)-4- ethyl-2,2- dimethyl- 1-oxa-4-azaspiro[5.5]- undecan-3-one 4.31 (B) 345.2

Example 45:((5s,8s)-8-[Benzyl(methyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-12-yl)(phenyl)methanone

Step 1.(5s,5s)-8-[Benzyl(methyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one.Following the methylation procedure described in Example 14, usingIntermediate 5A (856 mg, 2.85 mmol) as starting material, the titlecompound was obtained (609 mg, 68% yield)

Step 2. (5s,8s)-N-Benzyl-N-methyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-8-amine. To a solution of the product obtained in Step 1 (587 mg,1.87 mmol) in THF (2.3 mL), LiAlH₄ solution (5.6 mL, 1 M in THF, 5.6mmol) was added dropwise at 0-5° C. The reaction mixture was thenstirred at 50° C. overnight. Additional LiAlH₄ solution (1.9 mL, 1 M inTHF, 1.9 mmol) was added and it was again stirred at 50° C. overnight.1M NaOH and ethyl acetate were carefully added and the mixture wasfiltered through a pad of celite. The phases were separated and theaqueous phase was back extracted with ethyl acetate. The organic phaseswere combined, washed with water, dried over Na₂SO₄, filtered andconcentrated to dryness to give the title compound as a crude product(611 mg, overweight, quant, yield assumed).

Step 3. Title compound. To a solution of the product obtained in Step 2(560 mg, 1.87 mmol) in DCM (6.7 mL), cooled at 0° C., benzoyl chloride(0.26 mL, 2.24 mmol) and triethylamine (0.39 mL, 2.8 mmol) were addeddropwise under a nitrogen atmosphere. The reaction mixture was stirredat r.t. overnight, then NaHCO₃ sat. solution was added and it wasextracted with DCM. The organic phases were combined, washed with 1MNaOH, dried over Na₂SO₄, filtered and concentrated to dryness. Theresidue was purified by flash chromatography, silica gel, gradient DCMto MeOH:DCM (1:4) to give the title compound (563 mg, 74% yield).

HPLC retention time (method B): 4.64 min; MS: 405.2 (M+H).

Example 46:((5r,8r)-8-{Benzyl(methyl)amino}-4-oxa-12-azadispiro[2.1.5.3]tridecan-12-yl)(phenyl)methanone

The product was prepared according to the procedure described in Example45, using Intermediate 5B as starting material.

HPLC retention time (method B): 4.81 min; MS: 405.2 (M+H).

Examples 47 to 50 were prepared according to the procedure described inExample 21, using suitable starting materials:

Ret time MS EX Structure Chemical name (min) (M + H) 47

(6s,9s)-4-ethyl-9- (methylamino)-1- oxa-4- azaspiro[5.5]- undecan-3-oneacetate 0.66 227.1 48

(6s,9s)-4-ethyl- 2,2-dimethyl-9- (methylamino)-1- oxa-4- azaspiro[5.5]-undecan-3-one acetate 1.66 (B) 255.2 49

(6r,9r)-4-ethyl-2,2- dimethyl-9- (methylamino)-1- oxa-4- azaspiro[5.5]-undecan-3-one acetate 1.8  (B) 255.1 50

((5s,8s)-8- (methylamino)-4- oxa-12- azadispiro[2.1.5.3]- tridecan-12-yl)(phenyl)meth- anone acetate 2.48 (B) 315.2

Examples 51 to 60 were prepared according to the procedure described inExample 27, using suitable starting materials:

Ret time MS EX Structure Chemical name (min) (M + H) 51

(6s,9s)-4-ethyl-9- (methyl(phenethyl)- amino)-1-oxa-4- azaspiro[5.5]-undecan-3-one 3.34 (B) 331.2 52

(6s,9s)-4-ethyl-9- (isopentyl(methyl) amino)-1-oxa-4- azaspiro[5.5]-undecan-3-one 2.82 (B) 297.2 53

(6s,9s)-4-ethyl-9- (isopentyl(methyl) amino)-2,2- dimethyl-1-oxa-4-azaspiro[5.5]- undecan-3-one 3.29 (B) 325.2 54

(6s,9s)-4-ethyl-9- (isobutyl(methyl)- amino)-2,2- dimethyl-1-oxa-4-azaspiro[5.5]- undecan-3-one 3.15 (B) 311.2 55

(6s,9s)-4-ethyl- 2,2-dimethyl-9- (methyl(phenethyl)- amino)-1-oxa-4-azaspiro[5.5]- undecan-3-one 3.85 (B) 359.2 56

(6r,9r)-4-ethyl-2,2- dimethyl-9- (methyl(phenethyl)- amino)-1-oxa-4-azaspiro[5.5]- undecan-3-one 4.06 (B) 359.2 57

(6r,9r)-4-ethyl-9- (isopentyl(methyl) amino)-2,2- dimethyl-1-oxa-4-azaspiro[5.5]- undecan-3-one 3.45 (B) 325.3 58

((5s,8s)-8- [methyl(phenethyl)- amino]-4-oxa-12- azadispiro[2.1.5.3]-tridecan-12- yl)(phenyl)methanone 4.43 (B) 419.2 59

((5s,8s)-8- [isopentyl(methyl) amino]-4-oxa-12- azadispiro[2.1.5.3]-tridecan-12- yl)(phenyl)methanone 3.94 (B) 385.2 60

((5s,8s)-8- [isobutyl(methyl)- amino]-4-oxa-12- azadispiro[2.1.5.3]-tridecan-12- yl)(phenyl)methanone 3.78 (B) 371.2

Examples 61 to 68 were prepared according to the procedure described inStep 2 of Example 45, using suitable starting materials:

Ret time MS EX Structure Chemical name (min) (M + H) 61

(6s,9s)-4-ethyl-N- methyl-N- phenethyl-1-oxa- 4-azaspiro[5.5]-undecan-9-amine 3.68 (B) 317.2 62

(6s,9s)-N-benzyl- 4-ethyl-N,2,2- trimethyl-1-oxa-4- azaspiro[5.5]-undecan-9-amine 5.84 (B) 331.2 63

(6s,9s)-4-ethyl-N- isopentyl-N- methyl-1-oxa-4- azaspiro[5.5]-undecan-9-amine 3.10 (B) 283.3 64

(6s,9s)-4-ethyl-N- isopentyl-N,2,2- trimethyl-1-oxa-4- azaspiro[5.5]-undecan-9-amine 4.64 (B) 311.3 65

(6s,9s)-4-ethyl-N- isobutyl-N,2,2- trimethyl-1-oxa-4- azaspiro[5.5]-undecan-9-amine 4.52 (B) 297.3 66

(6s,9s)-4-ethyl- N,2,2-trimethyl-N- phenethyl-1-oxa- 4-azaspiro[5.5]-undecan-9-amine 5.26 (B) 345.3 67

(5s,8s)-12-benzyl- N-methyl-N-(2- phenylethyl)-4- oxa-12-azadispiro[2.1.5.3]- tridecan-8-amine 5.75  B) 405.3 68

(5s,8s)-12-benzyl- N-isobutyl-N- methyl-4-oxa-12- azadispiro[2.1.5.3]-tridecan-8-amine 5.14 (B) 357.3

Table of Examples with Binding to the σ₁-Receptor BIOLOGICAL ACTIVITYPharmacological Study

Human σ₁ Receptor Radioligand Assay

To investigate binding properties of test compounds to human σ₁receptor, transfected HEK-293 membranes and [³H](+)-pentazocine (PerkinElmer, NET-1056), as the radioligand, were used. The assay was carriedout with 7 μg of membrane suspension, 5 nM of [³H](+)-pentazocine ineither absence or presence of either buffer or 10 μM Haloperidol fortotal and non-specific binding, respectively. Binding buffer containedTris-HCl 50 mM at pH 8. Plates were incubated at 37° C. for 120 minutes.After the incubation period, the reaction mix was then transferred toMultiscreen HTS, FC plates (Millipore), filtered and plates were washed3 times with ice-cold 10 mM Tris-HCL (pH7.4). Filters were dried andcounted at approximately 40% efficiency in a MicroBeta scintillationcounter (Perkin-Elmer) using EcoScint liquid scintillation cocktail

Results:

As this invention is aimed at providing a compound or a chemicallyrelated series of compounds which act as ligands of the σ₁ receptor itis a very preferred embodiment in which the compounds are selected whichact as ligands of the σ₁ receptor and especially compounds which have abinding expressed as K_(i) which is preferably <1000 nM, more preferably<500 nM, even more preferably <100 nM.

The following scale as been adopted for representing the binding to theσ₁ receptor expressed as K_(i):

+K_(i)−σ₁>=500 nM

++K_(i)−σ₁<500 nM

+++K_(i)−σ₁<100 nM

All compounds prepared in the present application exhibit binding to theσ₁ receptor, in particular the following binding results are shown:

EX K_(i)-σ₁ 1 + 2 ++ 3 +++ 4 +++ 5 +++ 6 ++ 7 +++ 8 +++ 9 ++ 10 + 11 ++12 + 13 + 14 ++ 15 ++ 16 +++ 17 ++ 18 ++ 19 +++ 20 +++ 21 + 22 + 23 +24 + 25 + 26 + 27 ++ 28 ++ 29 ++ 30 +++ 31 +++ 32 +++ 33 ++ 34 +++ 35 ++36 + 37 + 38 ++ 39 + 40 + 41 ++ 42 +++ 43 +++ 44 ++ 45 +++ 46 ++ 47 +48 + 49 + 50 + 51 ++ 52 ++ 53 ++ 54 ++ 55 +++ 56 +++ 57 +++ 58 ++ 59 ++60 ++ 61 +++ 62 +++ 63 ++ 64 +++ 65 +++ 66 +++ 67 +++ 68 +++

The invention claimed is:
 1. A compound of general Formula (I):

m is 1, 2, 3, 4 or 5; n is 0, 1, 2, 3, 4 or 5; p is 0, 1 or 2; Y is—CH₂— or —C(O)—; X is a bond, —C(R_(x)R_(x′))—, —O—, —C(O)—, —C(O)NR₇,—NR₇C(O)— or —C(O)O—; wherein R_(x) is selected from the groupconsisting of halogen, —OR₇, substituted or unsubstituted C₁₋₆ alkyl,substituted or unsubstituted C₂₋₆ alkenyl and substituted orunsubstituted C₂₋₆ alkynyl; R_(x′) is selected from the group consistingof hydrogen, halogen, substituted or unsubstituted C₁₋₆ alkyl,substituted or unsubstituted C₂₋₆ alkenyl and substituted orunsubstituted C₂₋₆ alkynyl; R₇ is selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₆ alkyl, substituted orunsubstituted C₂₋₆ alkenyl and substituted or unsubstituted C₂₋₆alkynyl; R_(1′) is selected from the group consisting of substituted orunsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl,substituted or unsubstituted C₂₋₆ alkynyl, substituted or unsubstitutedcycloalkyl, substituted or unsubstituted aryl and substituted orunsubstituted heterocyclyl; R₂ is selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₆ alkyl, substituted orunsubstituted C₂₋₆ alkenyl, substituted or unsubstituted C₂₋₆ alkynyl,substituted or unsubstituted cycloalkyl, substituted or unsubstitutedaryl and substituted or unsubstituted heterocyclyl; R₃ and R_(3′) areindependently selected from the group consisting of hydrogen,substituted or unsubstituted C₁₋₆ alkyl, substituted or unsubstitutedC₂₋₆ alkenyl, substituted or unsubstituted C₂₋₆ alkynyl, substituted orunsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl,substituted or unsubstituted alkylaryl, substituted or unsubstitutedaryl, substituted or unsubstituted heterocyclyl or substituted orunsubstituted alkylheterocyclo; or R₃ and R_(3′), together with thecarbon atom to which they are attached, form a substituted orunsubstituted cycloalkyl; R₄ and R_(4′) are independently selected fromthe group consisting of hydrogen, substituted or unsubstituted C₁₋₆alkyl, substituted or unsubstituted C₂₋₆ alkenyl and substituted orunsubstituted C₂₋₆ alkynyl; R₅ and R_(5′) are independently selectedfrom the group consisting of hydrogen, substituted or unsubstituted C₁₋₆alkyl, substituted or unsubstituted C₂₋₆ alkenyl and substituted orunsubstituted C₂₋₆ alkynyl; or R₅ and R_(5′), together with the carbonatom to which they are attached, form a substituted or unsubstitutedcycloalkyl or a substituted or unsubstituted heterocyclyl; R₆ and R_(6′)are independently selected from the group consisting of hydrogen,halogen, substituted or unsubstituted C₁₋₆ alkyl, substituted orunsubstituted alkenyl, substituted or unsubstituted C₂₋₆ alkynyl, —CHOR₈and —C(O)OR₈; wherein R₈ is selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₆ alkyl, substituted orunsubstituted C₂₋₆ alkenyl and substituted or unsubstituted C₂₋₆alkynyl; R_(n) is selected from the group consisting of hydrogen,unsubstituted C₁₋₆ alkyl, unsubstituted C₂₋₆ alkenyl and unsubstitutedC₂₋₆ alkynyl; optionally as a stereoisomer, including enantiomers anddiastereomers, a racemate or a mixture of at least two stereoisomers,including enantiomers and/or diastereomers, in any mixing ratio, or acorresponding salt thereof, or a corresponding solvate thereof; with theproviso that when Y is —C(O)—; then R₁ is not


2. The compound according to claim 1, wherein X is a bond.
 3. Thecompound according to claim 1, wherein R_(1′) is selected from the groupconsisting of substituted or unsubstituted C₁₋₆ alkyl, substituted orunsubstituted C₂₋₆ alkenyl, substituted or unsubstituted C₂₋₆ alkynyl,substituted or unsubstituted cycloalkyl, substituted or unsubstitutedaryl and substituted or unsubstituted heterocyclyl.
 4. The compoundaccording to claim 3, wherein R_(1′) is substituted or unsubstitutedmethyl, substituted or unsubstituted ethyl or substituted orunsubstituted phenyl.
 5. The compound according to claim 1, wherein R₂is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₆ alkyl, substituted or unsubstituted C₂₋₆ alkenyl,substituted or unsubstituted C₂₋₆ alkynyl, substituted or unsubstitutedcycloalkyl, substituted or unsubstituted aryl and substituted orunsubstituted heterocyclyl.
 6. The compound according to claim 5,wherein R₂ is hydrogen, substituted or unsubstituted isopropyl,substituted or unsubstituted isobutyl or substituted or unsubstitutedphenyl.
 7. The compound according to claim 1, wherein R₃ and R_(3′),together with the carbon atom to which they are attached, form asubstituted or unsubstituted cycloalkyl.
 8. The compound according toclaim 7, wherein R₃ and R_(3′) form a substituted or unsubstitutedcyclopropyl.
 9. The compound according to claim 1, which is a compoundof Formula (I′)


10. The compound according to claim 1, which is a compound of Formula(I^(2′))


11. The compound according to claim 1, which is a compound of Formula(I^(3′))


12. The compound according to claim 1, which is selected from the groupconsisting of:(5s,8s)-8-(benzylamino)-12-ethyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one,(5r,8r)-8-(benzylamino)-12-ethyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one,(5s,8s)-12-ethyl-8-[methyl(2-phenylethyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one,(5r,8r)-12-ethyl-8-[methyl(2-phenylethyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one,(5s,8s)-8-[benzyl(methyl)amino]-12-ethyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one,(5s,8s)-12-ethyl-8-[(2-phenylethyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one,(5r,8r)-12-ethyl-8-[(2-phenylethyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one,(5s,8s)-8-[benzyl(methyl)amino]-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one,(5s,8s)-8-[methyl(2-phenylethyl)amino]-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one,(5s,8s)-8-(benzylamino)-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one,(5s,8s)-12-phenyl-8-[(2-phenylethyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one,(5r,8r)-8-(benzylamino)-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one,(5r,8r)-12-phenyl-8-[(2-phenylethyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one,(5r,8r)-8-[benzyl(methyl)amino]-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one,(5r,8r)-8-[methyl(2-phenylethyl)amino]-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one,(5r,8r)-8-[benzyl(methyl)amino]-12-ethyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one,(5s,8s)-N-benzyl-12-ethyl-N-methyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-8-amine,(5r,8r)-N-benzyl-12-ethyl-N-methyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-8-amine,(5s,8s)-N-benzyl-N-methyl-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-8-amine(5r,8r)-N-benzyl-N-methyl-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-8-amine,(5r,8r)-12-ethyl-8-(methylamino)-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-oneacetate,(5s,8s)-12-ethyl-8-(methylamino)-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-oneacetate,(5s,8s)-8-(methylamino)-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-oneacetate,(5r,8r)-8-(methylamino)-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-oneacetate,(5s,8s)-N-methyl-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-8-amineacetate,(5r,8r)-N-methyl-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-8-amineacetate,(5r,8r)-12-ethyl-8-[methyl(3-methylbutyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one,(5s,8s)-12-ethyl-8-[methyl(3-methylbutyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one,(5s,8s)-8-[methyl(3-methylbutyl)amino]-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one,(5r,8r)-8-[methyl(3-methylbutyl)amino]-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one,(5s,8s)-N-methyl-N-(3-methylbutyl)-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-8-amine,(5r,8r)-N-methyl-N-(3-methylbutyl)-12-phenyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-8-amine,(5s,8s)-12-ethyl-8-[methyl(2-methylpropyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-13-one,(5r,8r)-N-methyl-12-phenyl-N-(2-phenylethyl)-4-oxa-12-azadispiro[2.1.5.3]tridecan-8-amineand(5r,8r)-12-ethyl-N-methyl-N-(3-methylbutyl)-4-oxa-12-azadispiro[2.1.5.3]tridecan-8-amine.13. The compound according to claim 1, which is selected from the groupconsisting of:(6s,9s)-9-(benzylamino)-4-ethyl-1-oxa-4-azaspiro[5.5]undecan-3-one,(6r,9r)-9-(benzylamino)-4-ethyl-1-oxa-4-azaspiro[5.5]undecan-3-one,(6s,9s)-4-ethyl-9-(isobutyl(methyl)amino)-1-oxa-4-azaspiro[5.5]undecan-3-one,(6s,9s)-9-(benzylamino)-4-ethyl-2,2-dimethyl-1-oxa-4-azaspiro[5.5]undecan-3-one,(6r,9r)-9-(benzylamino)-4-ethyl-2,2-dimethyl-1-oxa-4-azaspiro[5.5]undecan-3-one,(6s,9s)-9-(benzyl(methyl)amino)-4-ethyl-1-oxa-4-azaspiro[5.5]undecan-3-one,(6r,9r)-9-(benzyl(methyl)amino)-4-ethyl-1-oxa-4-azaspiro[5.5]undecan-3-one,(6s,9s)-9-(benzyl(methyl)amino)-4-ethyl-2,2-dimethyl-1-oxa-4-azaspiro[5.5]undecan-3-one,(6r,9r)-9-(benzyl(methyl)amino)-4-ethyl-2,2-dimethyl-1-oxa-4-azaspiro[5.5]undecan-3-one,((5s,8s)-8-[Benzyl(methyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-12-yl)(phenyl)methanone,((5r,8r)-8-[Benzyl(methyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-12-yl)(phenyl)methanone,(6s,9s)-4-ethyl-9-(methylamino)-1-oxa-4-azaspiro[5.5]undecan-3-oneacetate,(6s,9s)-4-ethyl-2,2-dimethyl-9-(methylamino)-1-oxa-4-azaspiro[5.5]undecan-3-oneacetate,(6r,9r)-4-ethyl-2,2-dimethyl-9-(methylamino)-1-oxa-4-azaspiro[5.5]undecan-3-oneacetate,((5s,8s)-8-(methylamino)-4-oxa-12-azadispiro[2.1.5.3]tridecan-12-yl)(phenyl)methanoneacetate,(6s,9s)-4-ethyl-9-(methyl(phenethyl)amino)-1-oxa-4-azaspiro[5.5]undecan-3-one,(6s,9s)-4-ethyl-9-(isopentyl(methyl)amino)-1-oxa-4-azaspiro[5.5]undecan-3-one,(6s,9s)-4-ethyl-9-(isopentyl(methyl)amino)-2,2-dimethyl-1-oxa-4-azaspiro[5.5]undecan-3-one,(6s,9s)-4-ethyl-9-(isobutyl(methyl)amino)-2,2-dimethyl-1-oxa-4-azaspiro[5.5]undecan-3-one,(6s,9s)-4-ethyl-2,2-dimethyl-9-(methyl(phenethyl)amino)-1-oxa-4-azaspiro[5.5]undecan-3-one,(6r,9r)-4-ethyl-2,2-dimethyl-9-(methyl(phenethyl)amino)-1-oxa-4-azaspiro[5.5]undecan-3-one,(6r,9r)-4-ethyl-9-(isopentyl(methyl)amino)-2,2-dimethyl-1-oxa-4-azaspiro[5.5]undecan-3-one,((5s,8s)-8-[methyl(phenethyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-12-yl)(phenyl)methanone,((5s,8s)-8-[isopentyl(methyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-12-yl)(phenyl)methanone,((5s,8s)-8-[isobutyl(methyl)amino]-4-oxa-12-azadispiro[2.1.5.3]tridecan-12-yl)(phenyl)methanone,(6s,9s)-4-ethyl-N-methyl-N-phenethyl-1-oxa-4-azaspiro[5.5]undecan-9-amine,(6s,9s)-N-benzyl-4-ethyl-N,2,2-trimethyl-1-oxa-4-azaspiro[5.5]undecan-9-amine,(6s,9s)-4-ethyl-N-isopentyl-N-methyl-1-oxa-4-azaspiro[5.5]undecan-9-amine,(6s,9s)-4-ethyl-N-isopentyl-N,2,2-trimethyl-1-oxa-4-azaspiro[5.5]undecan-9-amine,(6s,9s)-4-ethyl-N-isobutyl-N,2,2-trimethyl-1-oxa-4-azaspiro[5.5]undecan-9-amine,(6s,9s)-4-ethyl-N,2,2-trimethyl-N-phenethyl-1-oxa-4-azaspiro[5.5]undecan-9-amine,(5s,8s)-12-benzyl-N-methyl-N-(2-phenylethyl)-4-oxa-12-azadispiro[2.1.5.3]tridecan-8-amineand(5s,8s)-12-benzyl-N-isobutyl-N-methyl-4-oxa-12-azadispiro[2.1.5.3]tridecan-8-amine.14. A process for the preparation of the compound according to claim 1,wherein when R₁ is —(CR₄R_(4′))_(p)R_(1′), which process comprises: a)the intramolecular cyclization of a compound of formula VII

or b) the reaction of a compound of formula XI

with a compound of formula XVI

or c) the incorporation of the group—N(R_(n))(CR₅R_(5′))_(m)X(CR₆R_(6′))_(n)R₂ by reaction of a ketone offormula VIIIK

with an amine of formula XVII

wherein R₁, R_(1′), R₂, R₃, R_(3′), R₄, R_(4′), R₅, R_(5′), R₆, R_(6′),R₇, R₈, R_(n), R_(x), R_(x′), m, n, p, X and Y have the meanings asdefined in claim 1 for the compound of Formula (I), LG represents aleaving group, including halogen, mesylate, tosylate and triflate, withthe proviso that when Y=CO, LG represents chloro or bromo, and Vrepresents an aldehyde or a leaving group, including halogen, mesylate,tosylate and triflate.
 15. A process for the preparation of the compoundaccording to claim 1, wherein Y is CH₂ and R₁ is —C(O)—R_(1′), whichprocess comprises: reacting a compound of formula XXXIV

with an acylating agent of formula XXXVI

wherein R_(1′), R₂, R₃, R_(3′), R₅, R_(5′), R₆, R_(6′), R₇, R₈, R_(n),R_(x), R_(x′), m, n and X have the meanings as defined in claim 1 forthe compound of Formula (I), and Z represents OH or halogen, includingbromo and chloro.
 16. A process for the preparation of the compound ofFormula (I) according to claim 1, employing a compound of Formula II,IIP, III, IIIP, XIII, XIIIP, XII, IV, V, VP, VI, XIV, XIVP, X, XP, VII,VHP, XV, XVP, XVK, XI, XIP, XIK, XVI, VIIIP, VIIIK, XVII, Ie, XXIP,XXIK, XXII, XVIIIP, XVIIIK, Ic, XIX, XIXP, XXP, XXK, XXIV, XXIVP, XXIVK,XXVI, XXVIP, XXVIK, XXIIIP, XXIIIK, Ig, XXVP, XXVK, Ih, XXVIIP, XXVIIK,XXVIIIa, XXIXP, XXIXK, XXVIIIb, XXXP, XXXK, XXVIIIc, XVIIIP, XVIIIK,XVII, Im, XXXIIIP, XXXIIIK, In, XXXVP, XXXVK, XXXII, XXXIIP, XXXIIK,XXXIV, XXXIVP, XXXVI, XXXVIIP, XXXVIIK, XXXP, XXXK, XXXIP, XXXIK or XVII

wherein R₁, R_(1′), R₂, R₃, R_(3′), R₄, R_(4′), R₅, R_(5′), R₆, R_(6′),R₇, R₈, R_(n), R_(x), R_(x′), m, n, p, X and Y have the meanings asdefined in claim 1 for the compound of Formula (I), LG represents aleaving group, including halogen, mesylate, tosylate and triflate, withthe proviso that when Y=CO, LG represents chloro or bromo, P′ representsa suitable protecting group, including 4-methoxybenzyl and benzyl, Qrepresents methyl or benzyl, and Z represents OH or halogen, includingbromo and chloro.
 17. A pharmaceutical composition which comprises thecompound according to claim 1, or a pharmaceutically acceptable saltthereof, and a pharmaceutically acceptable carrier, adjuvant or vehicle.18. A method of treating pain in a subject in need thereof, comprisingadministration of an effective amount of the compound according toclaim
 1. 19. The method according to claim 18, wherein the pain isselected from the group consisting of medium to severe pain, visceralpain, chronic pain, cancer pain, migraine, inflammatory pain, acutepain, neuropathic pain, allodynia and hyperalgesia.